Abstract MP45: Deletion Of The Transient Receptor Vanilloid-1 (TRPV1) Channel In Rats Attenuates 2 Kidney 1 Clip Hypertension

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Sean D Stocker ◽  
Leon J DeLalio
Keyword(s):  
Heart Rate ◽  
Renovascular Hypertension ◽  
Sensory Nerve ◽  
Experimental Models ◽  
Sensory Nerves ◽  
Male Rats ◽  
Wild Type ◽  
Renal Nerve ◽  
Trpv1 Channels ◽  
Arterial Blood

Renal denervation lowers arterial blood pressure (ABP) in both clinical populations and multiple experimental models of hypertension. This therapeutic effect is partly attributed to the removal of overactive renal sensory nerves that increase sympathetic efferent activity and ABP. Renal sensory nerves highly express TRPV1 channels, and administration of the TRPV1 agonist capsaicin increases renal sensory nerve activity. However, the extent by which TRPV1 channels directly contribute to renal nerve dependent models of hypertension has not been tested. To test this hypothesis, we generated a novel TRPV1 -/- rat using CRISPR/Cas9 and deletion of exon 3. Male and female TRPV1 -/- and wild-type littermates (8-12 weeks) were instrumented with telemetry. At 2 weeks later, renovascular hypertension via renal stenosis was produced by placement of a PTFE cuff (0.16 x 0.22 inches, 1mm long) around the right renal artery. Male TRPV1 -/- and wild-type rats had no differences in baseline mean ABP (99±2 vs 98±3 mmHg, respectively; n=7-9) or heart rate (390±7 vs 400±8 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, mean ABP was significantly lower at Day 28 in male TRPV1 -/- versus wild-type rats (125±8 vs 155±2 mmHg, respectively: P<0.01). Ganglionic blockade with chlorisondamine (2.5mg/kg, sc) at Day 28 produced a smaller fall in mean ABP of male TRPV1 -/- versus wild-type rats (-53±4 vs -86±3 mmHg, respectively; P<0.001). On the other hand, female TRPV1 -/- and wild-type rats had no differences in baseline mean ABP (102±2 vs 104±1 mmHg, respectively; n=6-9) or heart rate (419±8 vs 410±7 bpm, respectively). Renal stenosis significantly increased mean ABP in both groups; however, there were no differences at Day 28 between female TRPV1 -/- versus wild-type rats (117±8 vs 122±6 mmHg, respectively). Moreover, the increase in mean ABP was smaller in females versus males. The ganglionic blocker chlorisondamine produced similar depressor responses in female TRPV1 -/- versus wild-type rats (-64±7 vs -65±7 mmHg, respectively). These findings illustrate a sex difference in renovascular hypertension in rats, but importantly indicate that TRPV1 channels contribute to the established phase of renovascular hypertension in male rats.

Abstract MP48: Crispr/cas9 Trpv1 Deletion In Rats Does Not Impair Mechano- And Chemo-sensory Renal Afferent Nerve Responses

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Leon J DeLalio ◽  
Sean D Stocker
Keyword(s):  
Kidney Disease ◽  
Transient Receptor Potential ◽  
Sensory Nerve ◽  
Afferent Nerve ◽  
Sensory Nerves ◽  
Transient Receptor Potential Vanilloid ◽  
Wild Type ◽  
Trpv1 Channels ◽  
Arterial Blood ◽  
The Impact

Elevated renal afferent nerve activity (ARNA) or dysfunctional renal reflexes contributes to hypertension and chronic kidney disease. The transient receptor potential vanilloid type-1 (TRPV1) channel is expressed in renal sensory nerves, and intrarenal administration of the TRPV1 agonist capsaicin increases ARNA. Nonselective denervation of renal sensory nerves using high-concentration capsaicin reduces arterial blood pressure (ABP) in experimental models of hypertension. However, the role of TRPV1 channels in ARNA responses to chemo- and mechano-sensitive stimuli has not been directly tested. To test this hypothesis, we generated a novel TRPV1 rat knockout model (TRPV1 -/- ) using CRISPR/CAS9 to delete exon 3 . ARNA multifiber recordings were performed in male and female TRPV1 -/- and wild-type littermates (250-400g) after decerebration or Inactin anesthesia (data combined). Wild-type and TRPV1 -/- rats had no significant differences in baseline mean ABP (126±4 mmHg vs 138±5 mmHg, respectively; n=8-10) or heart rate (451±25 bpm vs 432±24 bpm, respectively; n=8-10). Baseline ARNA was not different between wild-type and TRPV1 -/- rats (16±3 Hz vs 28±6 Hz, respectively; n=8-10). Intrarenal artery infusion of the TRPV1 agonist capsaicin (0.1-10μM, 50μL per 15s) significantly increased ipsilateral ARNA in wild-type but not TRPV1 -/- rats (Δ discharge with 10μM: 65±3 Hz vs 6±1 Hz, respectively; n=5-7). As a second chemosensitive stimulus, intrarenal artery infusion of bradykinin (0.1-10μM, 50μL per 15s) produced similar increases in ipsilateral ARNA between wild-type and TRPV1 -/- rats (Δ discharge with 10μM: 52±6 Hz vs 73±18 Hz, respectively; n=5-6). Finally, elevated renal pelvic pressures (0-20mmHg; 30s) significantly increased ipsilateral ARNA in both wild-type and TRPV1 -/- rats; however, the ARNA response was significantly greater in TRPV1 -/- versus wild-type rats (Δ discharge with 20mmHg: 47±14 Hz versus 18±6 Hz, respectively; n=5-8). In conclusion, mechanosensitive and chemosensitive ARNA responses remain intact in TRPV1 -/- rats. The mechanisms responsible for renal sensory nerve activation remain unidentified and the impact of TRPV1 deletion in rat models of hypertension and kidney disease remains to be tested.

Abstract 034: Transient Receptor Potential Vanilloid-1 (TRPV1) Channels Mediate the Sympathoexcitatory and Pressor Responses to Central NaCl Stimulation

Hypertension ◽  
2014 ◽  
Vol 64 (suppl_1) ◽  
Author(s):  
Sean D Stocker ◽  
Sarah S Simmonds ◽  
Kirsteen N Browning
Keyword(s):  
Heart Rate ◽  
Broad Spectrum ◽  
Transient Receptor Potential ◽  
Cardiovascular Responses ◽  
Ruthenium Red ◽  
Transient Receptor Potential Vanilloid ◽  
Wild Type ◽  
Trpv1 Channels ◽  
Arterial Blood ◽  
Pressor Responses

Accumulating evidence indicates a high salt diet increases cerebrospinal fluid sodium concentration to elevate sympathetic nerve activity (SNA) and arterial blood pressure (ABP) in salt-sensitive hypertension. Recent evidence suggests TRPV1 channels underlie the ability of the brain to sense changes in osmotic pressure. The present study investigated whether the sympathoexcitatory response to intracerebroventricular (ICV) infusion of hypertonic NaCl was mediated by central TRPV1 channels. In Inactin-anesthetized Sprague-Dawley rats, ICV infusion of 1M NaCl (n=8) significantly increased lumbar SNA (140±12%), heart rate (20±7bpm), and mean ABP (9±1mmHg). ICV pretreatment with the broad-spectrum TRPV channel blocker ruthenium red (5mM, 2uL, n=8) eliminated the sympathoexcitatory response to ICV 1M NaCl: lumbar SNA (106±5%), heart rate (-6±7bpm), and mean ABP (1±2mmHg). Similarly, ICV pretreatment with the selective TRPV1 channel antagonist SB366791 (3mM, 2uL, n=8) prevented any change in lumbar SNA (106±3%), heart rate (4±6), and mean ABP (1±1mmHg). ICV injection of ruthenium red or SB366791 alone did not alter any variable. Surprisingly, ICV infusion of 1M NaCl (1μL) produced similar pressor responses in wild-type versus TRPV1-/- mice (12±2 vs 11±2 mmHg, n>4). Pretreatment with SB366791 attenuated the pressor response in wild-type but not TRPV1-/- mice. In vitro patch clamp recordings of neurons in the ventral lamina terminalis reveal that increases in bath osmolality produced dose-dependent membrane depolarization (5 mOsm: 5.0±0.63 mV, 10 mOsm: 6.1±1.24 mV, 15 mOsm: 12.4±2.1; n=5, P<0.05) and increase discharge frequency (5 mOsm: 208±32%, 10 mOsm: 246±55%, 15 mOsm: 274±101%, 20 mOsm: 496±53%; n=5, P<0.05). These responses were attenuated by bath application of the broad spectrum TRPV blocker ruthenium red. Collectively, these observations suggest that central TRPV channels mediate changes in neuronal excitability and cardiovascular responses to central osmotic stimulation.

scholarly journals Salt sensitivity of blood pressure in NKCC1-deficient mice

2008 ◽  
Vol 295 (4) ◽  
pp. F1230-F1238 ◽  
Author(s):  
Soo Mi Kim ◽  
Christoph Eisner ◽  
Robert Faulhaber-Walter ◽  
Diane Mizel ◽  
Susan M. Wall ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Wheel Running ◽  
Plasma Renin ◽  
Pressure Change ◽  
Standard Diet ◽  
Wild Type ◽  
Vascular Effects ◽  
Arterial Blood ◽  
Deficient Mice

NKCC1 is a widely expressed isoform of the Na-2Cl-K cotransporter that mediates several direct and indirect vascular effects and regulates expression and release of renin. In this study, we used NKCC1-deficient (NKCC1−/−) and wild-type (WT) mice to assess day/night differences of blood pressure (BP), locomotor activity, and renin release and to study the effects of high (8%) or low (0.03%) dietary NaCl intake on BP, activity, and the renin/aldosterone system. On a standard diet, 24-h mean arterial blood pressure (MAP) and heart rate determined by radiotelemetry, and their day/night differences, were not different in NKCC1−/− and WT mice. Spontaneous and wheel-running activities in the active night phase were lower in NKCC1−/− than WT mice. In NKCC1−/− mice on a high-NaCl diet, MAP increased by 10 mmHg in the night without changes in heart rate. In contrast, there was no salt-dependent blood pressure change in WT mice. MAP reductions by hydralazine (1 mg/kg) or isoproterenol (10 μg/mouse) were significantly greater in NKCC1−/− than WT mice. Plasma renin (PRC; ng ANG I·ml−1·h−1) and aldosterone (aldo; pg/ml) concentrations were higher in NKCC1−/− than WT mice (PRC: 3,745 ± 377 vs. 1,245 ± 364; aldo: 763 ± 136 vs. 327 ± 98). Hyperreninism and hyperaldosteronism were found in NKCC1−/− mice during both day and night. High Na suppressed PRC and aldosterone in both NKCC1−/− and WT mice, whereas a low-Na diet increased PRC and aldosterone in WT but not NKCC1−/− mice. We conclude that 24-h MAP and MAP circadian rhythms do not differ between NKCC1−/− and WT mice on a standard diet, probably reflecting a balance between anti- and prohypertensive factors, but that blood pressure of NKCC1−/− mice is more sensitive to increases and decreases of Na intake.

Renal sympathetic nerve activity modulates afferent renal nerve activity by PGE2-dependent activation of α1- and α2-adrenoceptors on renal sensory nerve fibers

2007 ◽  
Vol 293 (4) ◽  
pp. R1561-R1572 ◽  
Author(s):  
Ulla C. Kopp ◽  
Michael Z. Cicha ◽  
Lori A. Smith ◽  
Jan Mulder ◽  
Tomas Hökfelt
Keyword(s):  
Sensory Nerve ◽  
Nerve Fibers ◽  
Sensory Nerves ◽  
Nerve Activity ◽  
Renal Nerve ◽  
Renal Sympathetic Nerve Activity ◽  
Pelvic Wall ◽  
Renal Nerve Activity ◽  
Pelvic Perfusion ◽  
Renal Sympathetic

Increasing efferent renal sympathetic nerve activity (ERSNA) increases afferent renal nerve activity (ARNA). To test whether the ERSNA-induced increases in ARNA involved norepinephrine activating α-adrenoceptors on the renal sensory nerves, we examined the effects of renal pelvic administration of the α1- and α2-adrenoceptor antagonists prazosin and rauwolscine on the ARNA responses to reflex increases in ERSNA (placing the rat's tail in 49°C water) and renal pelvic perfusion with norepinephrine in anesthetized rats. Hot tail increased ERSNA and ARNA, 6,930 ± 900 and 4,870 ± 670%·s (area under the curve ARNA vs. time). Renal pelvic perfusion with norepinephrine increased ARNA 1,870 ± 210%·s. Immunohistochemical studies showed that the sympathetic and sensory nerves were closely related in the pelvic wall. Renal pelvic perfusion with prazosin blocked and rauwolscine enhanced the ARNA responses to reflex increases in ERSNA and norepinephrine. Studies in a denervated renal pelvic wall preparation showed that norepinephrine increased substance P release, from 8 ± 1 to 16 ± 1 pg/min, and PGE2 release, from 77 ± 11 to 161 ± 23 pg/min, suggesting a role for PGE2 in the norepinephrine-induced activation of renal sensory nerves. Prazosin and indomethacin reduced and rauwolscine enhanced the norepinephrine-induced increases in substance P and PGE2. PGE2 enhanced the norepinephrine-induced activation of renal sensory nerves by stimulation of EP4 receptors. Interaction between ERSNA and ARNA is modulated by norepinephrine, which increases and decreases the activation of the renal sensory nerves by stimulating α1- and α2-adrenoceptors, respectively, on the renal pelvic sensory nerve fibers. Norepinephrine-induced activation of the sensory nerves is dependent on renal pelvic synthesis/release of PGE2.

scholarly journals El entrenamiento de fuerza alivia las hipertrofias renal y cardíaca resultante de la hipertensión renovascular

2018 ◽  
Vol 0 (Avance Online) ◽  
Author(s):  
R Miguel-dos-Santos ◽  
JF Santos ◽  
FN Macedo ◽  
MB Almeida ◽  
VJ Santana-Filho ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Cardiac Hypertrophy ◽  
Strength Training ◽  
Renovascular Hypertension ◽  
Reduce Blood Pressure ◽  
The Body ◽  
Male Rats ◽  
Left Renal Artery ◽  
Beneficial Effects

Resumo Objetivo: Avaliar os efeitos do treinamento de força sobre as hipertrofias renal e cardíaca induzida pela hipertensão renovascular em ratos. Método: Dezoito ratos Wistar foram divididos em três grupos: Sham, hipertenso (2K1C) e hipertenso treinado (2K1C-TR). Os animais foram induzidos a hipertensão renovascular através da ligadura da artéria renal esquerda. O treinamento de força foi iniciado quatro semanas após a indução da hipertensão renovascular, teve duração de 12 semanas e foi realizado a 70% de uma repetição máxima. Ao final foi medida pressão arterial, frequência cardíaca e parâmetros das hipertrofias renal e cardíaca. Resultados: O treinamento de força promoveu a redução da frequência cardíaca (p=0.0025) e da pressão arterial (p=0.01). Além disso, o treinamento diminuiu as massas absolutas do rim (p=0.0001) e coração (p=0.006), e os índices de hipertrofias renal e cardíaca, tanto normalizado pela massa corporal dos animais (p=0.0001 e p=0.001, respectivamente) como normalizado pelo comprimento da tíbia (p=0.004 e p=0.0004, respectivamente). Conclusão: O treinamento de força tem efeitos benéficos na hipertensão renovascular em animais, sendo capaz de reduzir a pressão arterial e a frequência cardíaca, além de atenuar o desenvolvimento das hipertrofias renal e cardíaca em ratos com hipertensão renovascular. Resumen Objetivo: Evaluar los efectos del entrenamiento de fuerza sobre las hipertrofias renal y cardíaca inducidas por la hipertensión renovascular en ratas. Método: Dieciocho ratas se dividieron en tres grupos: simulado, hipertenso (2R1C) e hipertenso entrenado (2R1C-TR). Los animales fueron inducidos a la hipertensión renovascular a través de la ligadura de la arteria renal izquierda. El entrenamiento de fuerza se inició cuatro semanas después de la inducción de la hipertensión renovascular, duró 12 semanas y se realizó al 70% de una repetición máxima. Al final se midió la presión arterial, la frecuencia cardiaca y los parámetros de las hipertrofias renal y cardíaca. Resultados: El entrenamiento de fuerza promovió la reducción de la frecuencia cardíaca (p=0.0025) y la presión arterial (p=0.01). Además el entrenamiento disminuyó las masas absolutas de los riñones (p=0.0001) y el corazón (p=0.006), y los índices de hipertrofias renal y cardíaca, tanto normalizado por la masa corporal de los animales (p=0.0001 e p=0.001, respectivamente) como normalizado por la longitud de la tibia (p=0.004 e p=0.0004, respectivamente). Conclusión: El entrenamiento de fuerza tiene efectos beneficiosos en la hipertensión renovascular en animales, siendo capaz de reducir la presión arterial y la frecuencia cardíaca, además de atenuar el desarrollo de las hipertrofias renal y cardíaca en ratas con hipertensión renovascular. Abstract Objective: To evaluate the effects of strength training on renal and cardiac hypertrophy induced by the renovascular hypertension in rats. Method: Eighteen male rats were divided into three groups: sham, hypertensive (2K1C) and trained hypertensive (2K1C-TR). The animals were induced to renovascular hypertension through ligation of the left renal artery. Strength training was initiated four weeks after the induction of renovascular hypertension, had the duration of 12 weeks and was performed at 70% of one maximum repetition. At the end, it was measured blood pressure, heart rate and parameters of renal and cardiac hypertrophies. Results: Strength training promoted reduction in heart rate (p=0.0025) and blood pressure (p=0.01). In addition, training decreased the absolute masses of the kidney (p=0.0001) and heart (p=0.006), and the indexes of renal and cardiac hypertrophy, both normalized by the body mass of the animals (p=0.0001 e p=0.001, respectively) and by the length of the tibia (p=0.004 e p=0.0004, respectively). Conclusion: Strength training has beneficial effects on renovascular hypertension in animals, being able to reduce blood pressure and heart rate, attenuating the development of renal and cardiac hypertrophies in rats with renovascular hypertension.

scholarly journals Natriuretic peptides buffer renin-dependent hypertension

2014 ◽  
Vol 306 (12) ◽  
pp. F1489-F1498 ◽  
Author(s):  
Theo Demerath ◽  
Janina Staffel ◽  
Andrea Schreiber ◽  
Daniela Valletta ◽  
Frank Schweda
Keyword(s):  
Blood Pressure ◽  
Renovascular Hypertension ◽  
Natriuretic Peptide ◽  
Natriuretic Peptides ◽  
Plasma Renin ◽  
Control Mechanisms ◽  
Wild Type ◽  
Renal Vasoconstriction ◽  
Arterial Blood ◽  
Independent Effects

The renin-angiotensin-aldosterone system and cardiac natriuretic peptides [atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP)] are opposing control mechanisms for arterial blood pressure. Accordingly, an inverse relationship between plasma renin concentration (PRC) and ANP exists in most circumstances. However, PRC and ANP levels are both elevated in renovascular hypertension. Because ANP can directly suppress renin release, we used ANP knockout (ANP−/−) mice to investigate whether high ANP levels attenuate the increase in PRC in response to renal hypoperfusion, thus buffering renovascular hypertension. ANP−/− mice were hypertensive and had reduced PRC compared with that in wild-type ANP+/+ mice under control conditions. Unilateral renal artery stenosis (2-kidney, 1-clip) for 1 wk induced similar increases in blood pressure and PRC in both genotypes. Unexpectedly, plasma BNP concentrations in ANP−/− mice significantly increased in response to two-kidney, one-clip treatment, potentially compensating for the lack of ANP. In fact, in mice lacking guanylyl cyclase A (GC-A−/− mice), which is the common receptor for both ANP and BNP, renovascular hypertension was markedly augmented compared with that in wild-type GC-A+/+ mice. However, the higher blood pressure in GC-A−/− mice was not caused by disinhibition of the renin system because PRC and renal renin synthesis were significantly lower in GC-A−/− mice than in GC-A+/+ mice. Thus, natriuretic peptides buffer renal vascular hypertension via renin-independent effects, such as vasorelaxation. The latter possibility is supported by experiments in isolated perfused mouse kidneys, in which physiological concentrations of ANP and BNP elicited renal vasodilatation and attenuated renal vasoconstriction in response to angiotensin II.

Abstract MP21: Circadian Cycle Exaggerates Sympathoexcitatory Responses To Activation Of Chemosensitive Renal Sensory Nerves

Hypertension ◽  
2021 ◽  
Vol 78 (Suppl_1) ◽  
Author(s):  
Leon J DeLalio ◽  
Sean D Stocker
Keyword(s):  
Sympathetic Nerve Activity ◽  
Sensory Nerve ◽  
Sensory Nerves ◽  
Circadian Cycle ◽  
Nerve Activity ◽  
Arterial Infusion ◽  
Arterial Blood ◽  
Inactive Phase ◽  
The Impact ◽  
Circadian Patterns

Renal sensory nerves contribute to hypertension and renal dysfunction in chronic kidney disease. Selective chemokines (e.g., bradykinin or capsaicin) activate renal sensory nerves and produce reflexive efferent sympathetic nerve activity (SNA) and arterial blood pressure (ABP) responses. SNA, ABP, and renal function exhibit circadian patterns; yet the impact of circadian cycle on chemosensitive responses is unknown. We hypothesized that SNA and hemodynamic responses would be greater during the active phrase or nighttime versus the inactive phase or daytime. In Inactin anesthetized rats, simultaneous renal and splanchnic SNA and ABP were measured during intrarenal arterial infusion of capsaicin or bradykinin (0.1 μM - 30.0 μM; 50 μl over 15 s) at nighttime (N; 20:00-04:00; n= 12M, 10F) versus daytime (D; 09:00-16:00; n= 8M, 8F). Baseline mean ABP was significantly elevated during nighttime (N: 104±2 mmHg; D: 97±2 mmHg, p=0.04). Intrarenal capsaicin infusion produced concentration-dependent increases in renal and splanchnic SNA. Renal SNA increased more at nighttime versus daytime at 10 μM (N: 723±136 vs D: 409±79 %; p=0.03) and 30 μM (N: 826±181 vs D: 509±80 %; p=0.03). Similarly, splanchnic SNA was greater during nighttime versus daytime at 10 μM (N: 501±117 vs D: 204±53 %, p=0.03) and 30 μM (N: 537±101 vs D: 295±68 %; p=0.03). However, ABP responses were similar between nighttime versus daytime (30uM: 7±1 vs 6±1 mmHg, respectively). Intrarenal infusion of bradykinin produced concentration-dependent increases in renal and splanchnic SNA. Renal SNA increased more at nighttime versus daytime at 10 μM (N: 1773±216 vs D: 1249±112 %; p=0.01) and 30 μM (N: 2605±263 vs D: 1783±163 %; p=0.001). Similarly, splanchnic SNA was exaggerated at nighttime versus daytime at 0.1 μM (N: 163±65 vs D: 0±0 %; p=0.02), 1.0 μM (N: 566±114 vs D: 184±52 %; p=0.005), 10 μM (N: 1110±193 vs D: 583±87 %; p=0.006) and 30 μM (N: 2008±193 vs D: 1044±162 %; p<0.001). ABP response were similar between nighttime versus daytime at 30 μM (10±2 vs 6±1 mmHg, respectively). Circadian cycle exaggerates sympathoexcitatory responses produced by chemosensitive renal sensory nerve activation.

V1a and V1b Vasopressin Receptors Within the Paraventricular Nucleus Contribute to Hypertension in Male Rats Exposed to Chronic Mild Unpredictable Stress

2020 ◽  
Author(s):  
Dragana Komnenov ◽  
Harrison Quaal ◽  
Noreen F. Rossi
Keyword(s):  
Heart Rate ◽  
Paraventricular Nucleus ◽  
Rat Model ◽  
Pressor Response ◽  
Traditional Risk Factor ◽  
Male Rats ◽  
Mild Stress ◽  
Renal Nerve ◽  
Renal Sympathetic Nerve Activity ◽  
Vasopressin Receptors

Depression is an independent non-traditional risk factor for cardiovascular disease and mortality. The chronic unpredictable mild stress (CMS) rat model is a validated model of depression. Within the paraventricular nucleus (PVN), vasopressin (VP) via V1aR and V1bR have been implicated in stress and neurocardiovascular dysregulation. We hypothesized that in conscious, unrestrained CMS rats vs control, unstressed rats, PVN VP results in elevated arterial pressure (MAP), heart rate and renal sympathetic nerve activity (RSNA) via activation of V1aR and/or V1bR. Male rats underwent four weeks of CMS or control conditions. They were then equipped with hemodynamic telemetry transmitters, PVN cannula, and left renal nerve electrode. V1aR or V1bR antagonism dose-dependently inhibited MAP after VP injection. V1aR or V1bR blockers at their ED50 doses did not alter baseline parameters in either control or CMS rats, but attenuated the pressor response to VP microinjected into PVN by ~50%. Combined V­1aR and V1bR inhibition completely blocked the pressor response to PVN VP in control but not CMS rats. CMS rats required combined maximally inhibitory doses to block either endogenous VP within the PVN or responses to microinjected VP. Compared with unstressed control rats, CMS rats had higher plasma VP levels and greater abundance of V1aR and V1bR transcripts within PVN. Thus, the CMS rat model of depression results in higher resting MAP, heart rate and RSNA which can be mitigated by inhibition of vasopressinergic mechanisms involving both V1aR and V1bR within the PVN. Circulating VP may also play a role in the pressor response.

scholarly journals CaV3.2 T-type Ca2+ channels in H2S-mediated hypoxic response of the carotid body

2015 ◽  
Vol 308 (2) ◽  
pp. C146-C154 ◽  
Author(s):  
Vladislav V. Makarenko ◽  
Ying-Jie Peng ◽  
Guoxiang Yuan ◽  
Aaron P. Fox ◽  
Ganesh K. Kumar ◽  
...  
Keyword(s):  
Carotid Body ◽  
Sensory Nerve ◽  
Wild Type ◽  
Glomus Cells ◽  
Arterial Blood ◽  
Carotid Bodies ◽  
Intracellular Ca ◽  
Ca2 Channels ◽  
Body Response

Arterial blood O2 levels are detected by specialized sensory organs called carotid bodies. Voltage-gated Ca2+ channels (VGCCs) are important for carotid body O2 sensing. Given that T-type VGCCs contribute to nociceptive sensation, we hypothesized that they participate in carotid body O2 sensing. The rat carotid body expresses high levels of mRNA encoding the α1H-subunit, and α1H protein is localized to glomus cells, the primary O2-sensing cells in the chemoreceptor tissue, suggesting that CaV3.2 is the major T-type VGCC isoform expressed in the carotid body. Mibefradil and TTA-A2, selective blockers of the T-type VGCC, markedly attenuated elevation of hypoxia-evoked intracellular Ca2+ concentration, secretion of catecholamines from glomus cells, and sensory excitation of the rat carotid body. Similar results were obtained in the carotid body and glomus cells from CaV3.2 knockout ( Cacna1h−/−) mice. Since cystathionine-γ-lyase (CSE)-derived H2S is a critical mediator of the carotid body response to hypoxia, the role of T-type VGCCs in H2S-mediated O2 sensing was examined. Like hypoxia, NaHS, a H2S donor, increased intracellular Ca2+ concentration and augmented carotid body sensory nerve activity in wild-type mice, and these effects were markedly attenuated in Cacna1h−/− mice. In wild-type mice, TTA-A2 markedly attenuated glomus cell and carotid body sensory nerve responses to hypoxia, and these effects were absent in CSE knockout mice. These results demonstrate that CaV3.2 T-type VGCCs contribute to the H2S-mediated carotid body response to hypoxia.

Plasma catecholamines in rats during rewarming from induced hypothermia

1984 ◽  
Vol 57 (3) ◽  
pp. 808-814 ◽  
Author(s):  
S. B. Jones ◽  
F. Depocas ◽  
C. C. Chan
Keyword(s):  
Blood Pressure ◽  
Heart Rate ◽  
Carotid Artery ◽  
Plasma Catecholamines ◽  
Male Rats ◽  
Induced Hypothermia ◽  
Blood Samples ◽  
Arterial Blood ◽  
Colonic Temperature

The present study sought to quantitate the levels of plasma catecholamines [norepinephrine (NE), epinephrine (E), and dopamine (DA)] during induction and rewarming from hypothermia. Male rats (317 +/- 8 g) were made hypothermic by exposure to 0.9% halothane at -10 to -15 degrees C while blood pressure (carotid artery), heart rate, and colonic temperature (Tc) were monitored. Anesthesia was discontinued when Tc reached 28 degrees C. Tc continued to fall but was held at 20–20.5 degrees C for 30 min. Rewarming was then initiated by raising ambient temperature to 22 degrees C. Arterial blood samples were taken 1) before cooling, 2) just before rewarming, 3) when Tc reached 22 degrees C during rewarming, and 4) when Tc reached 27 degrees C during rewarming. Plasma was assayed radioenzymatically for catecholamines using both phenylethanolamine-N-methyltransferase and catechol-O-methyltransferase procedures, and hypothermic induction resulted in significant increases in NE, E, and DA above control levels (P less than 0.01). With rewarming to Tc = 22 degrees C, all catecholamines increased above the level observed during hypothermia (P less than 0.01), and NE and DA increased still further (P less than 0.01) when Tc reached 27 degrees C. The levels of plasma catecholamines observed during hypothermia and during the rewarming phase indicate a role of the sympathoadrenal medullary system in the metabolic adjustments associated with hypothermia and recovery. During rewarming, the levels of E and NE attained exceed those at which both substances may be expected to act as circulating hormones.

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