EFFECTS OF ANGIOTENSIN-CONVERTING ENZYME-INHIBITION ON ARTERIAL, VENOUS AND CAPILLARY FUNCTIONS IN CAT SKELETAL-MUSCLE IN-VIVO

The aim of the present study was to analyse quantitatively, on a cat g astrocnemius muscle preparation in vivo, the effects of local angioten sin-converting enzyme (ACE) inhibition by enalaprilat on total regiona l vascular resistance (tone) and its distribution to the large-bore ar terial resistance vessels (> 25 mu m), the small arterioles (< 25 mu m ) and the veins. Associated effects on capillary pressure and fluid ex change were also studied. Close-arterial infusion of enalaprilat (0.05 -0.20 mg kg muscle tissue min(-1)) elicited a moderate dilator respons e in all three consecutive sections of the muscle vascular bed. an inc rease in capillary pressure and transcapillary fluid filtration. This dilation could be abolished by the selective bradykinin B-2-receptor a ntagonist Hoe 140 (2 mg kg(-1) min(-1), i.a.). indicating that the dil ator mechanism of ACE inhibition was an increased local concentration of bradykinin. and hardly at ail a decreased concentration of angioten sin (AT) II. The generalized dilator response to ACE inhibition along the vascular bed suggested a relatively uniform distribution of ACE fr om artery to vein and this was further supported by the finding that a close-arterial infusion of AT I (0.04-0.32 mu g kg(-1) min(-1)), whic h was vasoactive only after conversion to AT ii by local ACE, elicited a generalized constrictor response in all three vascular sections. In contrast, infused AT ii (0.01-0.16 mu g kg(-1) min(-1)) constricted a lmost selectively the large-bore arterial vessels. The specific angiot ensin AT(1)-receptor antagonist losartan (2 mg kg(-1) min(-1). i.a.) a bolished the constrictor response to AT ii but did not affect vascular tone under control conditions, indicating that AT II is not involved in the initiation of basal vascular tone in muscle. These results, tak en together, indicate that under basal conditions vascular ACE contrib utes to the local control of vascular tone in skeletal muscle by degra ding the endogenous dilator bradykinin. and not by converting AT I int o vasoconstrictor AT ii.