Sensory denervation of the kidney attenuates renovascular hypertension in the rat

1986 ◽  
Vol 250 (1) ◽  
pp. H82-H86 ◽  
Author(s):  
J. M. Wyss ◽  
N. Aboukarsh ◽  
S. Oparil
Keyword(s):  
Blood Pressure ◽  
Renovascular Hypertension ◽  
Sensory Input ◽  
Sham Group ◽  
Left Renal Artery ◽  
Dorsal Rhizotomy ◽  
Afferent Nerves ◽  
Lower Blood ◽  
Sensory Denervation

To determine the role of the renal afferent nerves in the pathogenesis of one-kidney, one-clip renovascular hypertension, the renal afferent nerves were selectively lesioned by dorsal rhizotomy, a procedure that eliminates renal sensory input to the spinal cord but does not directly damage the sympathomotor innervation of the kidney. One week after denervation, the proximal left renal artery was clipped in denervated and sham control rats. Blood pressure of the sham group rose progressively over the next 5 wk, to 185 mmHg (systolic). In contrast, blood pressure of the denervated rats leveled off in the borderline hypertensive range, a level significantly lower than that of the sham group but significantly higher than that of non-clipped rats. In two further experiments the specificity of this effect was demonstrated. Lesion of the dorsal root nerves on the side of nephrectomy did not significantly lower blood pressure of non-clipped rats, and contralateral dorsal rhizotomy did not lower the blood pressure of clipped rats. These results demonstrate that the renal afferent nerves significantly contribute to one-kidney, one-clip renovascular hypertension in the rat.

Abstract 71: Novel Bach1 Modulators Increase HMOX1 and Suppress Hypertension in the Goldblatt Model of Renovascular Hypertension

Hypertension ◽  
2013 ◽  
Vol 62 (suppl_1) ◽  
Author(s):  
Matthew Kostura ◽  
Otis Attucks ◽  
Jareer Kassis ◽  
Suparna Gupta ◽  
Samuel Victory ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Enzyme Activity ◽  
Renovascular Hypertension ◽  
Transcriptional Repressor ◽  
Plasma Aldosterone ◽  
Lung Fibroblasts ◽  
Left Renal Artery ◽  
Dependent Manner ◽  
Sprague Dawley

We report for the first time a novel class of compounds that specifically modulate the Bach1 transcriptional repressor pathway. In cellula, the compounds selectively inhibit the activity of the transcriptional repressor Bach1 resulting in transcription of a network of antioxidant and cytoprotective genes including HMOX1. HPP-1971, a member of this class, is a potent and selective Bach1 inhibitor that induces HMOX1 > 40-fold with a potency of 408 nM in human lung fibroblasts. To assess activity in vivo, we tested HPP-1971 in the Goldblatt model of renovascular hypertension. Sprague Dawley rats were implanted with in dwelling pressure telemeter probes and subsequently underwent sham surgery or placement of a 0.25 mm silver clip around the left renal artery. HPP-1971 treatment, dosed orally at 1,3,10 and 30 mpk, commenced three days following clip surgery, and continued for 18 days. At study completion, blood pressure, clipped kidney weight, renal HMOX1 enzyme activity and plasma aldosterone levels were measured (see Table). HPP-1971 attenuated both kidney atrophy and the increase in blood pressure in a dose dependent manner with significant differences seen at 3, 10 and 30 mpk (p<.0001). HMOX1 enzyme activity in the clipped kidney increased with treatment, reaching a maximum of 5.7 ± 0.9 nM/hr/mg at 30 mpk relative to sham operated animals (p<.0001). Plasma aldosterone levels increased in 2K1C animals compared to sham controls but were reduced by HPP-1971 treatment. These findings define a novel role for Bach1 suppressors in counteracting the influence of the RAAS system on hypertension and kidney atrophy in the 2K1C model of renovascular hypertension.

scholarly journals MON-LB043 A Case of Renovascular Hypertension With Cortisol-Producing Adrenal Masses

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Takuya Higashitani ◽  
Daisuke Aono ◽  
Mitsuhiro Kometani ◽  
Shigehiro Karashima ◽  
Masashi Demura ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Blood Pressure ◽  
Renal Artery ◽  
Renovascular Hypertension ◽  
Plasma Glucose ◽  
Left Renal Artery ◽  
Glucose Levels ◽  
Computed Tomography Scanning ◽  
Old Japanese ◽  
Adrenal Masses

Abstract Renovascular hypertension (RVHT) is an important and potentially treatable form of resistant hypertension. Hypercortisolemia could also cause hypertension and diabetes mellitus. We experienced a case wherein adrenalectomy markedly improved blood pressure and plasma glucose levels in a patient with RVHT and subclinical Cushing’s syndrome. A 62-year-old Japanese man had been treated for hypertension and diabetes mellitus for 10 years. He was hospitalized because of disturbance in consciousness. His blood pressure (BP) was 236/118 mmHg; pulse rate, 132 beats/min; and plasma glucose level, 712 mg/dl. Abdominal computed tomography scanning revealed the presence of bilateral adrenal masses and left atrophic kidney. Abdominal magnetic resonance angiography demonstrated marked stenosis of the left main renal artery. The patient was subsequently diagnosed with atherosclerotic RVHT with left renal artery stenosis. Bilateral adrenal masses were immunohistologically identified as potential sites for cortisol overproduction. Therefore, laparoscopic left nephrectomy and adrenalectomy were simultaneously performed resulting in improved BP and glucose levels. Pathological studies revealed the presence of multiple cortisol-producing adrenal nodules and aldosterone-producing cell clusters in the adjacent left adrenal cortex. In the present case, activated renin-angiotensin-aldosterone system and cortisol overproduction resulted in severe hypertension, which was managed with simultaneous unilateral nephrectomy and adrenalectomy.

scholarly journals A reversal of fate : unravelling the role of central 5-HT in cardiorespiratory control in neonatal and adult rodents

2018 ◽  
Author(s):  
◽  
Jennifer Magnusson
Keyword(s):  
Blood Pressure ◽  
Physiological Role ◽  
Sudden Infant Death ◽  
Sudden Infant ◽  
Autonomic Tone ◽  
Neurogenic Hypertension ◽  
Cardiorespiratory Control ◽  
Arterial Blood ◽  
Lower Blood

We seek to address the extent to which a specific loss of 5-hydroxytryptamine (5-HT) affects the control of respiration, arterial blood pressure (ABP) and heart rate (HR) across vigilance-states based on existing evidence suggesting that 5-HT defects increase the risk for Sudden Infant Death Syndrome (SIDS) and neurogenic hypertension. SIDS is the leading cause of infant mortality between 1 month and 1 year of age, occurs during sleep, and up to 70% of all SIDS cases have at least one 5-HT system abnormality. Neonatal rodents lacking central 5-HT exhibit severe apneas, and a reduced ABP and HR. Central 5-HT has been implicated in the etiology of neurogenic hypertension, presumably due to projections of 5-HT neurons within the midline raphe to vagal and presympathetic regions of the brain. However, data from studies examining the specific role of central 5-HT function is conflicting or inconclusive. Neurogenic hypertension accounts for more than 90% of all hypertensive cases and the normal fall in ABP that occurs during non-rapid eye movement sleep is absent in some patients with hypertension. Understanding the mechanisms associated with the development of hypertension is critical not only to lower blood pressure, but to lower its associated cardiovascular events. The purpose of this dissertation is to examine the role of central 5-HT in the control of ABP during sleep and reveal, mechanistically, the physiological role of 5-HT in the autonomic control of ABP in neonatal and adult rodents. The overarching hypothesis for this dissertation is that central 5-HT is required for the maintenance of ABP and autonomic tone at rest in both neonatal and adult rodents.

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.

Blood pressure maintenance in NHE3-deficient mice with transgenic expression of NHE3 in small intestine

2005 ◽  
Vol 288 (3) ◽  
pp. R685-R691 ◽  
Author(s):  
William T. Noonan ◽  
Alison L. Woo ◽  
Michelle L. Nieman ◽  
Vikram Prasad ◽  
Patrick J. Schultheis ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Small Intestine ◽  
Transgenic Expression ◽  
Specific Effects ◽  
Lower Blood ◽  
Blood Pressures ◽  
Pressure Natriuresis ◽  
Deficient Mice ◽  
Robust Response

NHE3 Na+/H+ exchanger knockout ( Nhe3−/−) mice have severe absorptive deficits in the kidney proximal tubule and intestinal tract. The resulting hypovolemia has confounded efforts to carefully evaluate the specific effects of NHE3 deficiency on kidney function. Development of mice with transgenic expression of NHE3 in the small intestine (tg Nhe3−/−) has allowed us to analyze the role of renal NHE3 in overall maintenance of blood pressure, pressure natriuresis, and autoregulation of both glomerular filtration rate (GFR) and renal blood flow (RBF). Ambulatory blood pressure, measured by telemetry, was lower in tg Nhe3−/− mice than in wild-type controls (tg Nhe3+/+) when the mice were maintained on a normal NaCl diet but was normalized when they were provided with a high NaCl intake. Furthermore, administration of the AT1-receptor blocker losartan showed that circulating ANG II plays a major role in maintaining blood pressure in tg Nhe3−/− mice fed normal NaCl but not in those receiving high NaCl. Clearance studies revealed a blunted pressure-natriuresis response in tg Nhe3−/− mice at lower blood pressures but a robust response at higher blood pressures. Autoregulation of GFR and RBF was normal in tg Nhe3−/− mice. These results show that dietary NaCl loading normalizes blood pressure in awake tg Nhe3−/− mice and that alterations in NHE3 activity are not essential for normal autoregulation of GFR and RBF. Furthermore, the data strongly support the hypothesis that NHE3 plays an important role in the diuretic and natriuretic responses to increases in blood pressure but also show that mechanisms not involving NHE3 mediate pressure natriuresis in the higher range of blood pressures studied.

Interstitial Correction of Blood Volume Decrease during Hemodialysis

1989 ◽  
Vol 12 (10) ◽  
pp. 626-631 ◽  
Author(s):  
P.M. Kouw ◽  
P.M.J.M. De Vries ◽  
P.L Oe
Keyword(s):  
Blood Pressure ◽  
Blood Volume ◽  
Extracellular Fluid ◽  
Compensatory Mechanism ◽  
Fluid Shift ◽  
Lower Blood ◽  
Volume Blood ◽  
Dialysate Sodium ◽  
Volume Decrease

The etiology of hypotension during hemodialysis is multifactorial. Probably a decrease in blood volume caused by ultrafiltration, and acetate are both involved, while refilling from the interstitium acts as a compensatory mechanism. An osmotically induced transcellular fluid shift to intracellular might reduce the refilling capacity. This study investigated the effect of ultrafiltration on blood volume, blood pressure and refilling. The role of acetate and blood volume decrease in hypotension was established and intra- and extracellular fluid changes were calculated. Blood volume decrease depended on ultrafiltration: at high ultrafiltration rates refilling failed, apparently more so at high acetate plasma levels. An isolated blood volume decrease did not lower blood pressure. Concomitant high acetate levels caused hypotension and also seemed to reduce refilling. Nearly all refilling fluid came from the extracelullar compartment. Only high dialysate sodium concentrations gave rise to an intracellular loss.

scholarly journals Glucocorticoid receptor polymorphism in genetic hypertension

1998 ◽  
Vol 21 (1) ◽  
pp. 41-50 ◽  
Author(s):  
CJ Kenyon ◽  
M Panarelli ◽  
L Zagato ◽  
L Torielli ◽  
RP Heeley ◽  
...  
Keyword(s):  
Blood Pressure ◽  
Glucocorticoid Receptor ◽  
Female Rats ◽  
Male Rats ◽  
Adrenocortical Function ◽  
Lower Blood Pressure ◽  
Exon 2 ◽  
Lower Affinity ◽  
Lower Blood

The Milan hypertensive strain of rat (MHS) displays abnormalities in both renal function and adrenocortical activity. While the pressor role of the former has been studied in detail, the role of the latter has not yet been clearly evaluated. In the present study, glucocorticoid receptor (GR) binding characteristics in liver cytosol from adult MHS and Milan normotensive controls (MNS) have been investigated. Dexamethasone, aldosterone and corticosterone were bound with lower affinity to cytosol of MHS rats compared with that of MNS rats. This pattern of binding could explain the raised plasma corticosterone concentrations and adrenocortical hypertrophy previously noted in MHS. The coding sequence of MHS and MNS GR genes have been determined. The MHS gene differed in four respects from that of MNS: three silent point mutations and a polymorphic microsatellite region in exon 2. The latter polymorphism has been used in cosegregation studies of F2 hybrids of MHS x MNS. The MHS GR genotype was associated with hypercalciuria and lower blood pressure in female rats and lower body weight in male rats. Although the effect on blood pressure is small, it is consistent with the affinity data. MHS GR genotype cosegregated with lower blood pressure in F2 rats and displayed a lower affinity in binding studies. In conclusion, GR polymorphism may be responsible for differences of adrenocortical function between MHS and MNS. This may lead to a reduction in the blood pressure difference between the two strains.

Reversal of renovascular hypertension: role of the renal medulla

1987 ◽  
Vol 65 (8) ◽  
pp. 1566-1571 ◽  
Author(s):  
J. D. Swales ◽  
R. F. Bing ◽  
M. E. Edmunds ◽  
G. I. Russell ◽  
H. Thurston
Keyword(s):  
Blood Pressure ◽  
Renovascular Hypertension ◽  
Peripheral Resistance ◽  
Renin Angiotensin System ◽  
Renal Medulla ◽  
Pressure Control ◽  
Sodium Retention ◽  
Angiotensin System ◽  
Renin Angiotensin

The fall in blood pressure, which occurs when renovascular hypertension is corrected surgically, offers a means of elucidating the factors responsible for blood pressure control. When Goldblatt two-kidney, one-clip hypertension in the rat is reversed by unclipping the renal artery, or by removal of the ischaemic kidney, restoration of normal blood pressure is due to a fall in peripheral resistance. This is associated with sodium retention and cannot be modified by inhibition of the renin–angiotensin system. The fall is, however, partially inhibited by chemical removal of the renal medulla by means of 2-bromo-ethylamine hydrobromide. When normal rats are chemically medullectomized, moderate hypertension is produced, which cannot be attributed to the renin–angiotensin system or sodium retention. It is concluded that a renomedullary vasodepressor system is ablated by chemical medullectomy: further, this system plays a role in the surgical correction of Goldblatt hypertension.

Vascular collagen affects reactivity of hypertensive pulmonary arteries of the rat

1989 ◽  
Vol 66 (4) ◽  
pp. 1730-1735 ◽  
Author(s):  
C. A. Tozzi ◽  
G. J. Poiani ◽  
N. H. Edelman ◽  
D. J. Riley
Keyword(s):  
Blood Pressure ◽  
Pulmonary Arteries ◽  
Ang Ii ◽  
Lower Blood Pressure ◽  
Response Curves ◽  
Prostaglandin F2 Alpha ◽  
Lower Blood ◽  
Collagen Accumulation ◽  
Vasoactive Agonists

We studied the role of vascular collagen on the responsiveness of isolated pulmonary arteries to vasoactive agonists. Dose-response curves to prostaglandin F2 alpha, (PGF2 alpha), angiotensin II (ANG II), and norepinephrine (NE) and responses to a depolarizing concentration of KCl were obtained on rings of pulmonary artery from normal rats, chronically hypoxic (10% O2 for 10 days) rats, and chronically hypoxic rats treated with cis-4-hydroxy-L-proline (cHyp), an agent that blocks collagen accumulation. Treatment with this agent prevented the rise in pulmonary blood pressure normally seen during hypoxia. Collagen content was twice normal in hypoxic vessels and was significantly reduced in vessels from cHyp-treated hypoxic rats. There was no change in reactivity to PGF2 alpha, but reactivity to ANG II, NE, and KCl was decreased in vessels from hypoxic rats. cHyp treatment completely restored reactivity to NE and KCl and partially restored reactivity to ANG II. The changes in contractility could be a response to the lower blood pressure. Another explanation is that collagen deposited in hypertensive pulmonary arteries may impair reactivity to some constrictor agonists.

Endogenous opiate modulation of baroreflexes in normotensive and hypertensive rats

1988 ◽  
Vol 255 (5) ◽  
pp. H987-H991 ◽  
Author(s):  
J. E. Szilagyi
Keyword(s):  
Blood Pressure ◽  
Renovascular Hypertension ◽  
Baroreflex Sensitivity ◽  
Baroreceptor Reflex ◽  
Hypertensive Rats ◽  
Endogenous Opiates ◽  
Endogenous Opiate ◽  
The Brain ◽  
Naloxone Treatment

It is evident that hypertension is associated with elevated endogenous opiates. This study was designed to examine the role of endogenous opiates in the development and/or maintenance of two-kidney renovascular hypertension and in baroreceptor reflex function in conscious hypertensive rats. Naloxone administration during the onset of hypertension significantly attenuated the rise in blood pressure. After one week, systolic blood pressure in naloxone-treated rats was 27 mmHg lower than in 0.9% NaCl-treated hypertensive rats. Acute naloxone infusions in chronic hypertensive animals also significantly lowered blood pressure (-10%) and heart rate (-26%). Baroreceptor function was significantly enhanced in both normotensive (+135%) and hypertensive (+207%) rats after administration of naloxone. Furthermore, naloxone treatment also caused the baroreflex response to shift from the higher reset state toward that seen in normotensive counterparts. The inability of naloxone methyl bromide to alter baroreflex sensitivity indicates that the site(s) of action of opiates resides in the brain. These data support a role for opiates in the development and/or maintenance of renovascular hypertension, which may be related to alterations in baroreceptor reflex function.

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