Marked synergism between vasopressin and angiotensin II in a human isolated artery

Current scientific literature generally attributes the vasoconstrictor effects of [Arg(8)]vasopressin (AVP) to the activation of phospholipase C (PLC) and consequent release of Ca(2+) from the sarcoplasmic reticulum. However, half-maximal activation of PLC requires nanomolar concentrations of AVP, whereas vasoconstriction occurs when circulating concentrations of AVP are orders of magnitude lower. Using cultured vascular smooth muscle cells, we previously identified a novel Ca(2+) signaling pathway activated by 10-100 pM AVP. This pathway is distinguished from the PLC pathway by its dependence on protein kinase C (PKC) and L-type voltage-sensitive Ca(2+) channels (VSCC). In the present study, we used isolated, pressurized rat mesenteric arteries to examine the contributions of these different Ca(2+) signaling mechanisms to AVP-induced vasoconstriction. AVP (10(-14)-10(-6) M) induced a concentration-dependent constriction of arteries that was reversible with a V(1a) vasopressin receptor antagonist. Half-maximal vasoconstriction at 30 pM AVP was prevented by blockade of VSCC with verapamil (10 microM) or by PKC inhibition with calphostin-C (250 nM) or Ro-31-8220 (1 microM). In contrast, acute vasoconstriction induced by 10 nM AVP (maximal) was insensitive to blockade of VSCC or PKC inhibition. However, after 30 min, the remaining vasoconstriction induced by 10 nM AVP was partially dependent on PKC activation and almost fully dependent on VSCC. These results suggest that different Ca(2+) signaling mechanisms contribute to AVP-induced vasoconstriction over different ranges of AVP concentration. Vasoconstrictor actions of AVP, at concentrations of AVP found within the systemic circulation, utilize a Ca(2+) signaling pathway that is dependent on PKC activation and can be inhibited by Ca(2+) channel blockers.

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“…22). Our initial studies determined that responses to 30 pM and 10 nM AVP would not be altered by prior exposure to 30 pM AVP (data not shown).…”

Section: Acute Vasoconstriction Induced By 30 Pm and 10 Nm Avpmentioning

confidence: 99%

Vasopressin-induced vasoconstriction: two concentration-dependent signaling pathways

Henderson

Byron²

2007

Journal of Applied Physiology

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“…The present findings demonstrate that Ang II increases CCSM contraction as a pathological consequence of PBOO. We have used only one concentration of Ang II on each individual tissue strip as multiple application of Ang II to isolated human arteries results in a marked desensitization of the functional response (i.e., tachyphylaxis) [24]. This phenomenon may explain the large variation in the Ang II 10 -5 M error bar following PBOO (Figure 1).…”

Section: Discussionmentioning

confidence: 99%

Angiotensin II Increases Corpus Cavernosal Contractility and Oxidative Stress in Partial Bladder Outlet Obstructed Rabbits: Relevance to Erectile Dysfunction

Ertemi

Lau

Mikhailidis

et al. 2013

The Journal of Sexual Medicine

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Introduction We investigated the effect angiotensin II (Ang II), a corpus cavernosal smooth muscle (CCSM) constrictor peptide, has on tissue taken from rabbits following chronic partial bladder outlet obstruction (PBOO), as this model is characterized by an increase in corpus cavernosal collagen deposition and a marked reduction and impaired relaxation of CCSM cells. Aim To determine the interaction between Ang II and nitric oxide (NO) and the development of oxidative stress (OS) in a rabbit model of chronic PBOO. Methods Corpus cavernosal tissue was obtained from 12 sham-operated and 20 PBOO rabbits. Organ bath studies determined Ang II/NO interaction on CCSM function using losartan (AT1 receptor antagonist), sodium nitroprusside (SNP, NO donor), electrical field stimulation (EFS), and vardenafil (phosphodiesterase type 5 inhibitor). The role of OS in the Ang II response was also determined using diphenylene iodonium chloride (DPI), the nicotinamide adenine dinucleotide phosphate oxidase inhibitor, which inhibits superoxide production and superoxide dismutase (SOD, the enzyme that accelerates the breakdown of superoxide). Main Outcome Measure Action of Ang II and AT1 receptor antagonist, as well as SOD and DPI on CCSM function. Results Ang II caused a dose-dependent contraction of CCSM strips that was enhanced in PBOO rabbits and inhibited by losartan, DPI, and SOD. CCSM relaxation induced by SNP/EFS was impaired in this model and improved by vardenafil and losartan. Conclusions These findings imply that the increased Ang II contractile response is a pathological consequence of PBOO and that AT1 receptor inhibition may be a therapeutic approach to treat ED associated with PBOO.

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“…Recent work has shown that sympathetic denervation of the rat tail artery greatly increases the responsiveness of the isolated artery to ANG II and vasopressin by 2 wk after denervation (32). Both ANG II and vasopressin are significantly elevated during hypotensive hemorrhage and could conceivably provide a greater contribution to the maintenance of arterial pressure during prolonged hemorrhage in the denervated animal due to a similar denervation-induced supersensitivity to noncatecholamine vasopressor agents (13), although this possibility remains to be studied.…”

Section: Splanchnic Nerve Control Of Arterial Pressure During Hemorrhagementioning

confidence: 98%

Sympathetic innervation of the splanchnic region mediates the beneficial hemodynamic effects of 8-OH-DPAT in hemorrhagic shock

Tiniakov

Pahan

Scrogin

2012

American Journal of Physiology-Regulatory, Integrative and Comp

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Administration of the 5-HT(1A) receptor agonist, 8-OH-DPAT, improves cardiovascular hemodynamics and tissue oxygenation in conscious rats subjected to hypovolemic shock. This effect is mediated by sympathetic-dependent increases in venous tone. To determine the role of splanchnic nerves in this response, effects of 8-OH-DPAT (30 nmol/kg iv) were measured following fixed-arterial blood pressure hemorrhagic shock (i.e., maintenance of 50 mmHg arterial pressure for 25 min) in rats subjected to bilateral splanchnic nerve denervation (SD). Splanchnic denervation decreased baseline venous tone as measured by mean circulatory filling pressure (MCFP) and accelerated the onset of hypotension during blood loss. Splanchnic denervation did not affect the immediate pressor effect of 8-OH-DPAT but did reverse the drug's lasting pressor effect, as well as its ability to increase MCFP and improve metabolic acidosis. Like SD, adrenal demedullation (ADMX) lowered baseline MCFP and accelerated the hypotensive response to blood withdrawal but also reduced the volume of blood withdrawal required to maintain arterial blood pressure at 50 mmHg. 8-OH-DPAT raised MCFP early after administration in ADMX rats, but the response did not persist throughout the posthemorrhage period. In a fixed-volume hemorrhage model, 8-OH-DPAT continued to raise blood pressure in ADMX rats. However, it produced only a transient and variable rise in MCFP compared with sham-operated animals. The data indicate that 8-OH-DPAT increases venoconstriction and improves acid-base balance in hypovolemic rats through activation of splanchnic nerves. This effect is due, in part, to activation of the adrenal medulla.

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Marked synergism between vasopressin and angiotensin II in a human isolated artery

Cited by 13 publications

References 26 publications

Vasopressin-induced vasoconstriction: two concentration-dependent signaling pathways

Vasopressin-induced vasoconstriction: two concentration-dependent signaling pathways

Angiotensin II Increases Corpus Cavernosal Contractility and Oxidative Stress in Partial Bladder Outlet Obstructed Rabbits: Relevance to Erectile Dysfunction

Sympathetic innervation of the splanchnic region mediates the beneficial hemodynamic effects of 8-OH-DPAT in hemorrhagic shock

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