Effects of atriopeptin III on isolated mesenteric resistance vessels from SHR and WKY

Abstract

The effects of atriopeptin III (AP III) were determined on agonist-induced [i.e., 10(-4) M norepinephrine (NE)] and depolarization-induced (80 mM K+) contractions of isolated mesenteric resistance vessels (ID approximately 100 microns) from spontaneously hypertensive rats (SHR) and from normotensive control Wistar-Kyoto (WKY) rats. The vessels from both groups, when activated by 80 mM K+, were unaffected by AP III. However, activation of WKY vessels by 10(-4) M NE (both phasic and tonic contraction) was inhibited quite effectively and potently by AP III, whereas that in SHR vessels was much less inhibited. In the WKY rat vessels, the concentration of AP III that inhibited contraction by 50% for NE-induced phasic tension was 3.1 +/- 1.3 nM, whereas in SHR vessels it was nearly 1 microM. Comparison of AP III inhibition of NE-induced phasic tension to that at 5 min of activation (tonic tension) indicated that the tonic contractions were less sensitive to AP III than the phasic contractions in the vessels from both strains. A similar experiment indicated that AP III was a potent inhibitor of agonist-induced activation in a human renal resistance vessel (ID 125 microns) and that this vessel depended virtually completely on extracellular Ca2+ for NE-induced contraction. These studies contrast with earlier reports (1, 30) that similar peptides inhibited tension only in rat renal resistance vessels and not in resistance vessels from other vascular beds. The decreased sensitivity and efficacy of AP III in inhibiting tension in SHR compared with WKY mesenteric resistance vessels is discussed in the context of the etiology of spontaneous hypertension.

Action of probucol in arteries from normal and hypercholesterolaemic rabbits

“…The rings were then exposed to probucol (10-6 M -5 x 0-4 M) for 45 min before the addition of KCl or NA. The method used for assessing inhibitory effects of probucol on mesenteric resistance vessels was to contract the vessels with a submaximal concentration of KCl (80 mM) or NA (10-4 M), then wash the activating agent out and repeat the stimulus after 15 min of preincubation of the vessel with PSS containing probucol (Cauvin et al, 1987). Only one agonist was used in each experiment.…”

Atrial Natriuretic Peptide: Binding and Cyclic GMP Response in Cultured Vascular Smooth Muscle Cells From Spontaneously Hypertensive Rats

“…While we ourselves have no direct physiological data to support these conclusions, thoracic aorta 29,30 and mes enteric resistance 28 vessels from SHR have been demon strated to be significantly less sensitive to the relaxing actions of ANP. Therefore, altered ANP binding and transduction processes thereof in target tissues may be relevant to hypertension.…”

“…27 In contrast to whole body studies, investigations using isolated thoracic vessels clearly demonstrate reduced vasorelaxant responsiveness to ANP in SHR as com pared to WKY. [28][29][30] Reasons for the general opposite nature of hypertensive/normotensive sensitivity differ ences between isolated vessel and whole body study models are unclear. However, proposals have been made that exaggerated physiological responses to ANP in hypertensives (for whole body models) may relate to their hypertensive arterial 25 and/or renal 31 perfusion pressures.…”