Angiotensin II inhibits the forearm vascular response to increased arterial pressure in humans

Goldsmith, Steven R.; Hasking, Gregory J.

doi:10.1016/0735-1097(95)96225-n

“…16 Our results also verify the apparent divergence in the scientific literature that includes credible descriptions of both stimulatory 1,3,[17][18][19] and suppressive effects 5,8,20 of AII on the sympathetic nervous system. Finally, the enhancement of AII-dependent neuronal stimulation in the presence of the L-channel blocker nifedipine is consistent with the sympathoexcitation seen during long-term use of this agent in humans 21 and may help explain the potential adverse effects observed with calcium antagonists in high-risk patients.…”

Section: Discussionsupporting

confidence: 72%

Modulation of Angiotensin II Responses in Sympathetic Neurons by Cytosolic Calcium

Fernandez

¹

,

Huang

²

,

Davidson

³

et al. 2003

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Abstract-Both stimulatory and suppressive responses of the sympathetic nervous system to angiotensin II (AII) Key Words: sympathetic nervous system Ⅲ angiotensin II Ⅲ calcium Ⅲ calcium channel blockers Ⅲ norepinephrine Ⅲ inositol T he renin-angiotensin and sympathetic nervous systems are homeostatically interconnected by a complex series of mutually reinforcing and mutually inhibiting interactions. In general, each of these systems tends to reinforce the pressor effects of the other as the two systems act to defend arterial pressure. Sympathetic stimulation is a major controller of juxtaglomerular cell renin release through the actions of catecholamines on juxtaglomerular cell ␤ 1 receptors. 1 The angiotensin II (AII) subsequently generated in the bloodstream can exert positive feedback on sympathetic nervous activity by several complex mechanisms, including direct stimulatory actions of AII on central and peripheral sympathetic neuronal activity and catecholamine release. [1][2][3] In addition to its stimulatory effects, AII can also suppress sympathetic neuronal activity in vivo. In animals and humans, complex reflex inhibition occurs when increases in arterial pressure stimulate arterial baroreflexes to cause reflex suppression of sympathetic nervous outflow. A more confusing picture emerges in whole-animal experiments designed to isolate the contributions of the peripheral sympathetic nervous system: AII infusion can facilitate, 4 suppress, 5 or have no effect 6 on norepinephrine release from postganglionic sympathetic neurons. In humans, a similar pattern of sympathetic neural responses has been reported, with some studies showing increased norepinephrine spillover 3 and others showing no response 7 or decreased norepinephrine release 3,7,8 in response to AII. In other excitable cell types such as cardiomyocytes or vascular smooth muscle cells, a paradoxical response has also been reported. AII treatment was shown to increase cytosolic calcium ([Ca 2ϩ ]i) by stimulation of IP 3 -dependent pathways 9,10 and was also reported to decrease [Ca 2ϩ ]i through enhanced calcium efflux. 11,12 The current studies were undertaken to examine the effects of AII on neuronal [Ca 2ϩ ]i and to investigate whether alterations in [Ca 2ϩ ]i play a role in the apparent "bidirectional" excitatory and suppressive responses to AII seen in sympathetic neurons studied in vivo. Using isolated primary sympathetic neurons from rats, we first related neuronal responses to the dose of AII and to the baseline [Ca 2ϩ ]i. To confirm that the same neuron is capable of both stimulatory and suppressive responses to AII, cells with spontaneously low [Ca 2ϩ ]i were exposed to a Ca 2ϩ ionophore and cells with spontaneously high [Ca 2ϩ ]i were exposed to nifedipine. We used losartan to investigate the role of the AT 1 receptors and confirmed IP 3 pathway dependency with an IP 3 receptor blocker and by prior

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“…Thus 3 weeks of treatment with losartan in hypertensive patients resulted in a significant fall in blood pressure, but no significant changes in heart rate or HRV in the frequency domain, although cross-spectral analysis showed that BRS was significantly increased with losartan [25]. In humans, our studies have shown that cardiac vagal control is reduced by angiotensin II [3], and a facilitatory action on the baroreflex control of sympathetic activity has also been described [27]. The consistent lack of effect of AT " receptor antagonists on measures of cardiac autonomic control in humans might be considered surprising in view of the well described actions of angiotensin II and the results of studies with ACE inhibitors.…”

Section: Discussionmentioning

confidence: 58%

Effects of angiotensin II (AT1) receptor blockade on cardiac vagal control in heart failure

Vaile

¹

,

Chowdhary

²

,

Osman

³

et al. 2001

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The objective of the present study was to determine the autonomic effects of angiotensin II (AT(1)) receptor blocker therapy in heart failure. In a randomized double-blind cross-over study, we compared the effects of candesartan and placebo on baroreflex sensitivity and on heart rate variability at rest, during stress and during 24 h monitoring. Acute effects were assessed 4 h after oral candesartan (8 mg) and chronic effects after 4 weeks of treatment (dose titrated to 16 mg daily). The study group comprised 21 patients with heart failure [mean (S.E.M.) ejection fraction 33% (1%)], in the absence of angiotensin-converting enzyme (ACE) inhibitor therapy. We found that acute candesartan was not different from placebo in its effects on blood pressure or mean RR interval. Chronic candesartan significantly reduced blood pressure [placebo, 137 (3)/82 (3) mmHg; candesartan, 121 (4)/75 (2) mmHg; P<0.001; values are mean (S.E.M.)], but had no effect on mean RR interval [placebo, 857 (25) ms; candesartan, 857 (21) ms]. Compared with placebo there were no significant effects of acute or chronic candesartan on heart rate variability in the time domain and no consistent effects in the frequency domain. Baroreflex sensitivity assessed by the phenylephrine bolus method was significantly increased after chronic candesartan [placebo, 3.5 (0.5) ms/mmHg; candesartan, 4.8 (0.7) ms/mmHg; P<0.05], although there were no changes in cross-spectral baroreflex sensitivity. Thus, in contrast with previous results with ACE inhibitors, angiotensin II receptor blockade in heart failure did not increase heart rate variability, and there was no consistent effect on baroreflex sensitivity.

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“…Central and peripheral actions resulting in inhibition of cardiac parasympathetic control and facilitation of sympathetic activity have been demonstrated in animals [6][7][8]. In humans, our studies have shown that cardiac vagal control is reduced by angiotensin II [3], and a facilitatory action on the baroreflex control of sympathetic activity has also been described [27]. These actions appear to be mediated by AT " receptors [28], and therefore pharmacological blockade might be expected to increase measures of cardiac vagal activity and reduce those related to sympathetic activity.…”

Section: Discussionmentioning

confidence: 52%

Effects of angiotensin II (AT1) receptor blockade on cardiac vagal control in heart failure

VAILE¹,

CHOWDHARY²,

OSMAN³

et al. 2001

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The objective of the present study was to determine the autonomic effects of angiotensin II (AT(1)) receptor blocker therapy in heart failure. In a randomized double-blind cross-over study, we compared the effects of candesartan and placebo on baroreflex sensitivity and on heart rate variability at rest, during stress and during 24 h monitoring. Acute effects were assessed 4 h after oral candesartan (8 mg) and chronic effects after 4 weeks of treatment (dose titrated to 16 mg daily). The study group comprised 21 patients with heart failure [mean (S.E.M.) ejection fraction 33% (1%)], in the absence of angiotensin-converting enzyme (ACE) inhibitor therapy. We found that acute candesartan was not different from placebo in its effects on blood pressure or mean RR interval. Chronic candesartan significantly reduced blood pressure [placebo, 137 (3)/82 (3) mmHg; candesartan, 121 (4)/75 (2) mmHg; P<0.001; values are mean (S.E.M.)], but had no effect on mean RR interval [placebo, 857 (25) ms; candesartan, 857 (21) ms]. Compared with placebo there were no significant effects of acute or chronic candesartan on heart rate variability in the time domain and no consistent effects in the frequency domain. Baroreflex sensitivity assessed by the phenylephrine bolus method was significantly increased after chronic candesartan [placebo, 3.5 (0.5) ms/mmHg; candesartan, 4.8 (0.7) ms/mmHg; P<0.05], although there were no changes in cross-spectral baroreflex sensitivity. Thus, in contrast with previous results with ACE inhibitors, angiotensin II receptor blockade in heart failure did not increase heart rate variability, and there was no consistent effect on baroreflex sensitivity.

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Angiotensin II inhibits the forearm vascular response to increased arterial pressure in humans

Cited by 9 publications

References 8 publications

Modulation of Angiotensin II Responses in Sympathetic Neurons by Cytosolic Calcium

Modulation of Angiotensin II Responses in Sympathetic Neurons by Cytosolic Calcium

Effects of angiotensin II (AT1) receptor blockade on cardiac vagal control in heart failure

Effects of angiotensin II (AT1) receptor blockade on cardiac vagal control in heart failure

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