Effects of cyclic AMP‐affecting agents on contractile reactivity of isolated mesenteric and renal resistance arteries of the rat

Abstract

1 Effects of adenosine 3': 5'-cyclic monophosphate (cyclic AMP)-affecting agents were compared in mesenteric and renal resistance arteries that had been isolated from 20 week old Wistar-Kyoto rats, chemically sympathectomized, stretched to their optimal diameter for mechanical performance and made to contract in response to 30 mm potassium. 2 In mesenteric resistance arteries, isoprenaline, dopamine, NaF, forskolin, isobutyl-methylxanthine, milrinone and dibutyryl-cyclic AMP induced relaxation. Clonidine induced further increases in tension that could be reduced by pertussis toxin and prazosin but not by yohimbine. Clonidine also reduced relaxant responses to isoprenaline. 3 In renal resistance arteries, isoprenaline and dopamine failed to induce relaxation. Compared to mesenteric resistance arteries, renal vessels were less sensitive to the relaxant effect of NaF, forskolin and isobutyl-methylxanthine. Relaxant responses to dibutyryl-cyclic AMP did not differ between the two resistance arteries. 4 Indirect evidence thus suggests that in mesenteric resistance arteries, adenylate cyclase is susceptible to pharmacological activation and inhibition and is functionally coupled to relaxation. The refractory nature of renal resistance arteries to the relaxant effects of isoprenaline and dopamine could be due primarily to absence of appropriate receptors and to a relatively low activity of adenylate cyclase.

A molecular signature in the pannexin1 intracellular loop confers channel activation by the α1 adrenoreceptor in smooth muscle cells

“…The Rho kinase pathway is therefore a possible target in this pathway; however, the specificity for α1AR would need elucidation. Furthermore, phenylephrine-mediated constriction has also been linked to activation of a G i –cAMP (adenosine 3′,5′-monophosphate)–dependent signaling pathway in rat mesenteric arteries (50, 51) and swine renal arteries (52), and pharmacological evidence has demonstrated a possible interaction between α1AR and the G i pathway in promoting cardiomyocyte contraction (53). Although our work shows that purinergic signaling is a key component to the α1AR vasoconstriction pathway, the mechanism linking α1AR stimulation and Panx1 channel opening requires more detailed analysis of the signaling pathways downstream of α1AR, 5-HT 2A , 5-HT 1B/1D , and ET A .…”

Dopamine D 1 Receptor Augmentation of D 3 Receptor Action in Rat Aortic or Mesenteric Vascular Smooth Muscles

“…47,48 It seems paradoxical that the D 3 receptor dilates the mesenteric artery because D 2 -like receptors decrease while D 1 -like receptors increase cAMP production. 1-3 D 3 receptors linkage to adenylyl cyclase inhibition is weak, unless adenylyl cyclase V is present.…”

Physiological control of splanchnic blood flow by adrenaline: studies during acute hypoglycaemia in man

“…α-Adrenoceptor agonists, such as phenylephrine and noradrenaline, cause mesenteric and hepatic artery vasoconstriction that can be blocked by α-adrenergic blockade in rats, cats and dogs [12,17]. The non-selective β-agonist isoprenaline increases mesenteric and hepatic artery blood flow in dogs, cats, man and rats [12,[18][19][20][21][22].…”