Hypotensive effect of ANG II and ANG-(1–7) at the caudal ventrolateral medulla involves different mechanisms

2002 ◽  
Vol 283 (5) ◽  
pp. R1187-R1195 ◽  
Author(s):  
A. C. Alzamora ◽  
R. A. S. Santos ◽  
M. J. Campagnole-Santos
Keyword(s):  
Nitric Oxide ◽  
Arterial Pressure ◽  
Specific Inhibitor ◽  
Hypotensive Effect ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Caudal Ventrolateral Medulla ◽  
Before And After ◽  
Male Wistar Rats ◽  
Vascular Tonus

The objective of the present study was to determine the contribution of the autonomic nervous system and nitric oxide to the depressor effect produced by unilateral microinjection of ANG-(1–7) and ANG II into the caudal ventrolateral medulla (CVLM). Unilateral microinjection of ANG-(1–7), ANG II (40 pmol), or saline (100 nl) was made into the CVLM of male Wistar rats anesthetized with urethane before and after intravenous injection of 1) methyl-atropine, 2.5 mg/kg; 2) prazosin, 25 μg/kg; 3) the nitric oxide synthase (NOS) inhibitor, N G-nitro-l-arginine methyl ester (l-NAME), 5 mg/kg; or 4) the specific inhibitor of neuronal NOS, 7-nitroindazole (7-NI), 45 mg/kg. Arterial pressure and heart rate (HR) were continuously monitored. Microinjection of ANG-(1–7) or ANG II into the CVLM produced a significant decrease in mean arterial pressure (MAP; −11 ± 1 mmHg, n = 12 and −10 ± 1 mmHg, n= 10, respectively) that was not accompanied by consistent changes in HR or in cardiac output. The effect of ANG-(1–7) was abolished after treatment with methyl-atropine (−3 ± 0.6 mmHg, n = 9) or l-NAME (−2.3 ± 0.5 mmHg, n = 8) or 7-NI (−2.8 ± 0.6 mmHg, n = 5). In contrast, these treatments did not significantly interfere with the ANG II effect (−10 ± 2.6 mmHg, n = 8; −8 ± 1.5 mmHg, n = 8; and −12 ± 3.6 mmHg, n = 6; respectively). Peripheral treatment with prazosin abolished the hypotensive effect of ANG-(1–7) and ANG II. Microinjection of saline did not produce any significant change in MAP or in HR. These results suggest that the hypotensive effect produced by ANG II at the CVLM depends on changes in adrenergic vascular tonus and, more importantly, the hypotensive effect produced by ANG-(1–7) also involves a nitric oxide-related mechanism.

Effects of endothelium-derived relaxing factor and nitric oxide on rat mesangial cells

1990 ◽  
Vol 258 (1) ◽  
pp. F162-F167 ◽  
Author(s):  
P. J. Shultz ◽  
A. E. Schorer ◽  
L. Raij
Keyword(s):  
Nitric Oxide ◽  
Superoxide Dismutase ◽  
Mesangial Cells ◽  
Specific Inhibitor ◽  
Ang Ii ◽  
Glomerular Mesangial Cells ◽  
Functional Responses ◽  
Cross Sectional ◽  
Relaxing Factor ◽  
Endothelium Derived Relaxing Factor

We have investigated whether endothelium-derived relaxing factor (EDRF) and nitric oxide (NO), a substance proposed to be one of the EDRFs, could elicit biochemical and biological responses in rat glomerular mesangial cells (MC). In wells with MC alone, guanosine 3',5'-cyclic monophosphate (cGMP) levels were 2.6 +/- 0.6 fmol/microgram protein, and bradykinin did not affect these levels, whereas in coincubation experiments with bovine aortic EC and rat MC, cGMP levels in MC increased to 44.6 +/- 21 fmol/micrograms protein after bradykinin stimulation (P less than 0.05). This effect was potentiated by superoxide dismutase and inhibited by hemoglobin and L-NG-monomethyl arginine, a specific inhibitor of EDRF synthesis. Increases in cGMP were also observed when MC were incubated directly with NO and were potentiated by superoxide dismutase and inhibited by hemoglobin. We also tested whether NO could inhibit angiotensin II (ANG II)-induced reductions in cross-sectional area (CSA) of MC. When MC were exposed to ANG II only, 65% of the cells underwent a significant reduction in CSA, as measured by digital image analysis. However, when MC were incubated with ANG II and NO, only 10% of cells responded (P less than 0.04). These studies demonstrate that EDRF and NO induce significant biochemical and functional responses in rat glomerular MC and suggest that communication between EC and MC may be important in regulation of glomerular function.

Baroreflex modulation by angiotensins at the rat rostral and caudal ventrolateral medulla

2006 ◽  
Vol 290 (4) ◽  
pp. R1027-R1034 ◽  
Author(s):  
Andréia C. Alzamora ◽  
Robson A. S. Santos ◽  
Maria J. Campagnole-Santos
Keyword(s):  
Heart Rate ◽  
Baroreflex Sensitivity ◽  
Opposite Effect ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Differential Modulation ◽  
Baroreflex Control ◽  
Caudal Ventrolateral Medulla ◽  
Angiotensin Peptides ◽  
Reflex Bradycardia

We determined the effect of microinjection of ANG-(1–7) and ANG II into two key regions of the medulla that control the circulation [rostral and caudal ventrolateral medulla (RVLM and CVLM, respectively)] on baroreflex control of heart rate (HR) in anesthetized rats. Reflex bradycardia and tachycardia were induced by increases and decreases in mean arterial pressure produced by intravenous phenylephrine and sodium nitroprusside, respectively. The pressor effects of ANG-(1–7) and ANG II (25 pmol) after RVLM microinjection (11 ± 0.8 and 10 ± 2 mmHg, respectively) were not accompanied by consistent changes in HR. In addition, RVLM microinjection of these angiotensin peptides did not alter the bradycardic or tachycardic component of the baroreflex. CVLM microinjections of ANG-(1–7) and ANG II produced hypotension (−11 ± 1.5 and −11 ± 1.9 mmHg, respectively) that was similarly not accompanied by significant changes in HR. However, CVLM microinjections of angiotensins induced differential changes in the baroreflex control of HR. ANG-(1–7) attenuated the baroreflex bradycardia (0.26 ± 0.06 ms/mmHg vs. 0.42 ± 0.08 ms/mmHg before treatment) and facilitated the baroreflex tachycardia (0.86 ± 0.19 ms/mmHg vs. 0.42 ± 0.10 ms/mmHg before treatment); ANG II produced the opposite effect, attenuating baroreflex tachycardia (0.09 ± 0.06 ms/mmHg vs. 0.31 ± 0.07 ms/mmHg before treatment) and facilitating the baroreflex bradycardia (0.67 ± 0.16 ms/mmHg vs. 0.41 ± 0.05 ms/mmHg before treatment). The modulatory effect of ANG II and ANG-(1–7) on baroreflex sensitivity was completely abolished by peripheral administration of methylatropine. These results suggest that ANG II and ANG-(1–7) at the CVLM produce a differential modulation of the baroreflex control of HR, probably through distinct effects on the parasympathetic drive to the heart.

scholarly journals Brain Prostaglandin D2 Increases Neurogenic Pressor Activity and Mean Arterial Pressure in Angiotensin II-Salt Hypertensive Rats

Hypertension ◽  
2019 ◽  
Vol 74 (6) ◽  
pp. 1499-1506 ◽  
Author(s):  
Ninitha Asirvatham-Jeyaraj ◽  
A. Daniel Jones ◽  
Robert Burnett ◽  
Gregory D. Fink
Keyword(s):  
Cerebrospinal Fluid ◽  
Angiotensin Ii ◽  
Mean Arterial Pressure ◽  
Arterial Pressure ◽  
Developmental Stage ◽  
Rostral Ventrolateral Medulla ◽  
Ventrolateral Medulla ◽  
Ang Ii ◽  
Salt Hypertension ◽  
Pressor Activity

This study tested whether brain L-PGDS (lipocalin-type prostaglandin [PG] D synthase), through prostanoid signaling, might increase neurogenic pressor activity and thereby cause hypertension. Sprague Dawley rats on high-salt diet received either vehicle or Ang II (angiotensin II) infusion. On day 4, the developmental stage of hypertension, brains from different sets of control and Ang II–treated rats were collected for measuring L-PGDS expression, PGD2 levels, and DP1R (type 1 PGD2 receptor) expression. In a different set of 14-day Ang II-salt–treated rats, mini-osmotic pumps were used to infuse either a nonselective COX (cyclooxygenase) inhibitor ketorolac, L-PGDS inhibitor AT56, or DP1R inhibitor BWA868C to test the role of brain COX-PGD2-DP1R signaling in Ang II-salt hypertension. The acute depressor response to ganglion blockade with hexamethonium was used to quantify neurogenic pressor activity. During the developmental stage of Ang II-salt hypertension, L-PGDS expression was higher in cerebrospinal fluid, and PGD2 levels were increased in the choroid plexus, cerebrospinal fluid, and the cardioregulatory brain region rostral ventrolateral medulla. DP1R expression was decreased in rostral ventrolateral medulla. Both brain COX inhibition with ketorolac and L-PGDS inhibition with AT56 lowered mean arterial pressure by altering neurogenic pressor activity compared with vehicle controls. Blockade of DP1R with BWA868C, however, increased the magnitude of Ang II-salt hypertension and significantly increased neurogenic pressor activity. In summary, we establish that the development of Ang II-salt hypertension requires increased COX- and L-PGDS–derived PGD2 production in the brain, making L-PGDS a possible target for treating neurogenic hypertension.

Angiotensin II modulates arterial baroreflex function via a central alpha 1-adrenoceptor mechanism in rabbits

1995 ◽  
Vol 269 (5) ◽  
pp. R1009-R1016 ◽  
Author(s):  
Y. Nishida ◽  
K. L. Ryan ◽  
V. S. Bishop
Keyword(s):  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Ang Ii ◽  
Arterial Baroreflex ◽  
Baroreflex Control ◽  
Renal Sympathetic Nerve Activity ◽  
Baroreflex Function ◽  
Before And After ◽  
Dose Dependent ◽  
Renal Sympathetic

To test the hypothesis that angiotensin II (ANG II) modulates arterial baroreflex function via a central alpha 1-adrenoceptor mechanism, we examined the effects of intravertebral infusion of ANG II on baroreflex function curves before and after intravertebral administration of the alpha 1-adrenoreceptor antagonist prazosin. Rabbits were chronically instrumented with subclavian and vertebral arterial catheters, venous catheters, and aortic and vena caval occludes. Baroreflex curves were obtained by relating heart rate (HR) to mean arterial pressure during increases and decreases in arterial pressure. Intravertebral infusions of ANG II (5, 10, and 20 ng.kg-1.min-1) produced a dose-dependent shift of the midrange of the curve toward higher pressures (64 +/- 1 to 68 +/- 1, 76 +/- 1, and 85 +/- 2 mmHg, respectively). Pretreatment with prazosin (10 micrograms/kg) via the vertebral artery markedly reduced the shift in the baroreflex curve induced by the highest dose of ANG II (64 +/- 2 to 70 +/- 2 mmHg). These data suggest that ANG II resets the operating point of the HR baroreflex curve to a higher blood pressure and that this effect is mediated via a central alpha 1 mechanism. When the effects of vertebral ANG II on the baroreflex control of renal sympathetic nerve activity (RSNA) were examined, intravertebral administration of ANG II, while reducing the gain and the maximum RSNA, did not reset the RSNA baroreflex curve. These data suggest that ANG II acutely resets the HR baroreflex but not the RSNA baroreflex and that the resetting involves an alpha 1-adrenergic mechanism.

Effects of blockade of brain angiotensin II receptors in conscious, sodium-deprived dogs

1983 ◽  
Vol 245 (6) ◽  
pp. R881-R887 ◽  
Author(s):  
V. L. Brooks ◽  
I. A. Reid
Keyword(s):  
Angiotensin Ii ◽  
Arterial Pressure ◽  
Intravenous Infusion ◽  
Plasma Renin ◽  
Hypotensive Effect ◽  
Similar Degree ◽  
Central Action ◽  
Ang Ii ◽  
Sodium Deficiency ◽  
Low Sodium Diet

The present studies were designed to evaluate the physiological significance of the actions of angiotensin II (ANG II) on the brain. The effects of blockade of brain ANG II receptors by intracarotid or intravertebral infusions of saralasin were studied in conscious dogs with high circulating ANG II levels (142 +/- 16 pg/ml) due to a low-sodium diet. Three doses of saralasin were infused into each pair of arteries and intravenously: 0.1, 0.3, and 1.0 micrograms X kg-1 X min-1. Saralasin produced dose-related decreases in arterial pressure during infusion into the carotid or vertebral arteries, confirming that ANG II maintains arterial pressure during sodium deficiency. However, intravenous saralasin administration decreased pressure to a similar degree, suggesting that the hypotensive effect was due to recirculation of saralasin, rather than to blockade of a central action of circulating ANG II. Heart rate was not altered by infusion of saralasin by any route. Saralasin administration also caused a dose-dependent increase in plasma renin activity and plasma ANG II concentration. However, because the increases produced by intracarotid or intravertebral saralasin did not differ from the increase produced by intravenous infusion, these results do not provide evidence that renin release is modulated by a central action of ANG II during sodium deficiency. Plasma corticosteroid levels were reduced (2.4 +/- 0.5 to 1.4 +/- 0.2 micrograms/dl, P less than 0.05) by intravenous infusion of the highest dose of saralasin, but neither intracarotid nor intravertebral saralasin infusion altered plasma corticosteroid concentration.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Cerebral Blood Flow Changes during Cortical Spreading Depression are Not Altered by Inhibition of Nitric Oxide Synthesis

1994 ◽  
Vol 14 (6) ◽  
pp. 939-943 ◽  
Author(s):  
Zheng Gang Zhang ◽  
Michael Chopp ◽  
Kenneth I. Maynard ◽  
Michael A. Moskowitz
Keyword(s):  
Nitric Oxide ◽  
Blood Pressure ◽  
Arterial Blood Pressure ◽  
Cortical Spreading Depression ◽  
Spreading Depression ◽  
Arterial Blood ◽  
Nos Inhibitors ◽  
Before And After ◽  
Male Wistar Rats

CBF increases concomitantly with cortical spreading depression (CSD). We tested the hypothesis that CBF changes during CSD are mediated by nitric oxide (NO). Male Wistar rats (n = 23) were subjected to KCl-induced CSD before and after administration of nitric oxide synthase (NOS) inhibitors N-nitro-l-arginine (L-NNA) or N-nitro-l-arginine methyl ester (L-NAME) and in nontreated animals. CBF, CSD, and mean arterial blood pressure were recorded. Brain NOS activity was measured in vitro in control, L-NNA, and L-NAME-treated rats by the conversion of [3H]arginine to [3H]citrulline. Our data show that the NOS inhibitors did not significantly change regional CBF (rCBF) during CSD, even though cortical NOS activity was profoundly depressed and systemic arterial blood pressure was significantly increased. Our data suggest that rCBF during CSD in rats is not regulated by NO.

Caudal ventrolateral medulla can alter vasopressin and arterial pressure

1985 ◽  
Vol 14 (3) ◽  
pp. 227-232 ◽  
Author(s):  
Alan F. Sved ◽  
William W. Blessing ◽  
Donald J. Reis
Keyword(s):  
Arterial Pressure ◽  
Ventrolateral Medulla ◽  
Caudal Ventrolateral Medulla

NITROGEN OXIDE ROLE IN MANIFESTATION OF RESPIRATORY EFFECTS OF INCREASED EXOGENOUS IL-1Β LEVEL IN BLOOD-VASCULAR SYSTEM

2019 ◽  
pp. 91-102
Author(s):  
A.A. Klinnikova ◽  
G.A. Danilova ◽  
N.P. Aleksandrova
Keyword(s):  
Nitric Oxide ◽  
Intravenous Administration ◽  
Inflammatory Cytokine ◽  
Vascular System ◽  
Specific Inhibitor ◽  
External Respiration ◽  
Respiratory Effects ◽  
Before And After ◽  
Keywords Cytokines ◽  
Ventilation Response

The purpose of the study is to identify the role of nitrergic mechanisms in the ability of the pro-inflammatory cytokine IL-1β to influence the respiration pattern and hypoxic ventilation response. Materials and Methods. The experiments were performed on 42 anesthetized rats. To conduct an inhibitory analysis of the nitric oxide role in the manifestation of IL-1β respiratory effects, the authors used a non-selective inhibitor of NO-synthases of Nitro-L-arginine-methyl ether (L-NAME), and a highly specific inhibitor of inducible nitric oxide synthase, aminoguanidine bicarbonate. The hypoxic ventilation response was evaluated by a rebreathing method with a hypoxic gas mixture before and after intravenous administration of human recombinant IL-1β. Pneumatic tachometry was used to register the parameters of external respiration. Results. Intravenous administration of IL-1β has an activating effect on respiration and causes an increase in tidal volume by 36±5.2 %, minute respiration volume by 23±3.8 % and average inspiratory flow rate by 20±3.0 %. However, an increase in IL-1β systemic level decreases the ventilation response to hypoxia. Inhibition of NO-synthase activity with both L-NAME and aminoguanidine reduces IL-1β respiratory effects. Conclusion. One of the mechanisms to implement the respiratory effects of the key pro-inflammatory cytokine IL-1β in case of increase in its circulating level is an increase in the synthesis of nitric oxide with vascular endothelium cells. Keywords: cytokines, interleukin-1β, ventilation, ventilation response to hypoxia, hypoxic chemoreflex, nitric oxide. Цель исследования. Выявление роли нитрергических механизмов в способности провоспалительного цитокина ИЛ-1β оказывать влияние на паттерн дыхания и гипоксический вентиляционный ответ. Материалы и методы. Эксперименты выполнены на 42 наркотизированных крысах. Для проведения ингибиторного анализа роли оксида азота в проявлении респираторных эффектов ИЛ-1β использовались неселективный ингибитор NO-синтаз L-нитро-аргинин-метилэфира (L-NAME), а также высокоспецифичный ингибитор индуцибельной синтазы оксида азота аминогуанидина бикарбоната. Гипоксический вентиляционный ответ оценивался методом возвратного дыхания гипоксической газовой смесью до и после внутривенного введения человеческого рекомбинантного ИЛ-1β. Для регистрации параметров внешнего дыхания использовался метод пневмотахометрии. Результаты. Показано, что внутривенное введение ИЛ-1β оказывает активирующее влияние на дыхание, вызывая увеличение дыхательного объема на 36,0±5,2 %, минутного объема дыхания – на 23,0±3,8 % и средней скорости инспираторного потока – на 20,0±3,0 %. Вместе с тем повышение системного уровня ИЛ-1β вызывает ослабление вентиляционного ответа на гипоксию. Ингибирование NO-синтазной активности с помощью как L-NAME, так и аминогуанидина ослабляет респираторные эффекты ИЛ-1β. Выводы. Одним из механизмов реализации респираторных эффектов ключевого провоспалительного цитокина ИЛ-1β при повышении его циркулирующего уровня является усиление синтеза оксида азота клетками сосудистого эндотелия. Ключевые слова: цитокины, интерлейкин-1β, вентиляция, вентиляционный ответ на гипоксию, гипоксический хеморефлекс, оксид азота.

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