Angiotensin II facilitates sympathetic transmission in rat hind limb circulation.

Abstract

We developed a novel method to stimulate the sympathetic innervation of the isolated, perfused rat hind limb to investigate whether a subpressor concentration of angiotensin II (Ang II) facilitates noradrenergic transmission in the vascular bed to skeletal muscle. We electrically stimulated the lumbar sympathetic trunk while perfusing the preparation with artificial medium. Seventy-five percent of the resulting frequency-dependent increases in perfusion pressure were mediated by <x,-adrenergic receptors. Ang II (10 nM) significantly enhanced the effects of nerve stimulation at 1 and 10 Hz (by 42% and 35%, respectively). At a supramaximal stimulation frequency (20 Hz), Ang II prolonged the duration of the response without changing the peak increase in pressure. The reuptake inhibitor cocaine did not influence the effects of Ang II at 1 and 10 Hz but blocked the effect at 20 Hz. To control for nonspecific synergism with norepinephrine, we compared Ang II with vasopressin. Both peptides potentiated the pressor response to exogenous norepinephrine; however, vasopressin did not change the pressor response to nerve stimulation at any frequency. We conclude that Ang II, but not vasopressin, facilitates noradrenergic transmission in skeletal muscle resistance vessels, independent of its direct vasoconstrictor activity. The neurovascular preparation we describe may be useful in addressing other hypotheses concerning sympathetic transmission in skeletal muscle resistance vessels. 8 Evidence indicating that Ang II enhances noradrenergic transmission was derived from experiments in cardiac tissue, large-caliber vessels, mesenteric artery or tail artery preparations, and various vascular beds. However, no conclusive data are available for the skeletal muscle vasculature, which is a major determinant of total peripheral resistance.9 In a recent report, Schwieler et al 10 were unable to find any influence of Ang II on noradrenergic transmission in a blood-perfused canine skeletal muscle.The available, circumstantial evidence for an interaction between Ang II and sympathetic transmission in skeletal muscle resistance vessels was derived from studies on pithed rat preparations.111 However, recent data suggest that in the pithed rat, the observed actions of Ang II on the pressor response evoked by electrical stimulation of the spinal cord are largely, if not entirely, due to the elevation of basal blood pressure induced by Ang II.11 Such an effect is nonspecific, as opposed to specific effects mediated by interactions with the sympathetic transmission.We tested the hypothesis that Ang II enhances the pressor response induced by stimulation of the sympathetic nerves supplying a skeletal muscle resistance vessel bed. We developed a method to stimulate the sympathetic innervation of the isolated rat hindquarter, which we perfused with an artificial medium. To exclude nonspecific synergism between pressor agents, we used a subpressor concentration of Ang II and compared Ang II with arginine vasopressin (AVP). AVP had no specific eff...

Arginine Vasopressin Enhances Sympathetic Constriction Through the V 1 Vasopressin Receptor in Human Saphenous Vein

“…In contrast to the present results, Hilgers et al 18 did not find any effect of AVP on sympathetic transmission in an in vitro perfused rat hind limb preparation. A common finding in the vascular effects of this peptide is the heterogeneity of responsiveness depending on regional and species differences 28,29 and may be due to different populations or sensitivity of receptor sites for AVP.…”

“…A common finding in the vascular effects of this peptide is the heterogeneity of responsiveness depending on regional and species differences 28,29 and may be due to different populations or sensitivity of receptor sites for AVP. 6,8,30 In addition, Hilgers et al 18 used only one concentration of AVP (0.3 nmol/L), which probably was insufficient to modulate neurogenic responses. Because the present findings show that the potentiating effects of AVP are concentration dependent, it is conceivable that differences between the concentrations of AVP used may also account for the discrepant findings of our study and those of Hilgers et al 18 Some of the present observations may be of clinical significance.…”

“…[15][16][17] However, in other studies, AVP did not change the constrictor activity of the peripheral sympathetic nervous system. 18 In the human forearm, AVP attenuates phenylephrine-induced vasoconstriction, 19 whereas recent experiments in human isolated mesenteric arteries show that AVP enhances adrenergic-mediated responses. 20 Currently, there is no information concerning the modulating effects of AVP on human veins.…”

Involvement of nitric oxide, but not prostaglandins, in the vascular sympathoinhibitory effects of losartan in the pithed spontaneously hypertensive rat

“…More recently, the same finding has been extended to All AT,-receptor antagonists (Wong et al, 1991;Moreau et al, 1993). As All is known to potentiate the sympathetic nervous system both centrally and in the periphery (Starke, 1971;Grant & McGrath, 1988) and to increase plasma noradrenaline levels through stimulation of prejunctional AT,-receptors (Hilgers et al, 1993;Brower & Janicki, 1994), inhibition of endogenous All synthesis and blockade of All AT,-receptors have been pro-1 Author for correspondence posed as the mechanisms underlying the sympathoinhibitory effects of ACE inhibitors and AT,-receptor antagonists, respectively.…”

“…Many in vitro and in vivo studies support the concept tht All facilitates the sympathetic neuronal function (Starke, 1971;Hilgers et al, 1993). However, a positive interaction between All and the sympathetic neurones has been easier to demonstrate for those controlling vascular smooth muscle tone than for those controlling heart rate (Antonaccio & Kerwin, 1981;Hatton & Clough, 1982;Lanier & Malik, 1983;Vollmer et al, 1984).…”