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: Character ization of the muscarinic receptor mediating vasodilation and the poss ible hypertension-induced effects on the nature of this receptor, whic h have both received little attention in resistance vessels of the SHR . Methods: After a methoxamine-induced vasoconstriction, the vessels w ere dilated with acetyl-beta-metacholine (MCh). The MCh-induced vasodi lation was analysed by means of the M(1)-selective antagonist pirenzep ine, 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 comp ounds was quantified by means of pA(2) values. Atropine, a non-selecti ve muscarinic antagonist, was used for comparison. Results: The rank o rder of potency for the muscarinic receptor antagonists in preparation s taken from SHR and WKY rats appears to be atropine > 4-DAMP > pFHHSi D > pirenzepine > AQ-RA 741 > AF-DX 116. This rank order corresponds t o that found in isolated conduit arteries. Conclusions: The pA(2) valu es for the various compounds were not significantly different in SHR a nd WKY rat preparations, indicating that the nature of this receptor i s not influenced by hypertension. The high potency of the M(3)-selecti ve drugs and the weak activity of pirenzepine and the M(2)-selective a ntagonists suggest a major role of M(3)-receptors in the cholinergic v asodilation in the perfused mesenteric vascular bed both in SHR and WK Y rat preparations.