CHARACTERIZATION OF THE MUSCARINIC RECEPTORS IN THE MESENTERIC VASCULAR BED OF SPONTANEOUSLY HYPERTENSIVE RATS

Objective: The nature of the muscarinic (M) receptor subtype mediating endothelium-dependent vasodilation was investigated in Wistar-Kyoto (WKY) rats and spontaneously hypertensive rats (SHR). Design: Characterization of the muscarinic receptor mediating vasodilation and the possible hypertension-induced effects on the nature of this receptor, which have both received little attention in resistance vessels of the SHR. Methods: After a methoxamine-induced vasoconstriction, the vessels were dilated with acetyl-beta-metacholine (MCh). The MCh-induced vasodilation was analysed by means of the M(1)-selective antagonist pirenzepine, the M(2)-selective antagonists AF-DX 116 and AQ-RA 741 and the M(3)-selective antagonists 4-DAMP and pFHHSiD. The potency of these compounds was quantified by means of pA(2) values. Atropine, a non-selective muscarinic antagonist, was used for comparison. Results: The rank order of potency for the muscarinic receptor antagonists in preparations taken from SHR and WKY rats appears to be atropine > 4-DAMP > pFHHSiD > pirenzepine > AQ-RA 741 > AF-DX 116. This rank order corresponds to that found in isolated conduit arteries. Conclusions: The pA(2) values for the various compounds were not significantly different in SHR and WKY rat preparations, indicating that the nature of this receptor is not influenced by hypertension. The high potency of the M(3)-selective drugs and the weak activity of pirenzepine and the M(2)-selective antagonists suggest a major role of M(3)-receptors in the cholinergic vasodilation in the perfused mesenteric vascular bed both in SHR and WKY rat preparations.