Long-term treatment with angiotensin converting enzyme inhibitor restores reduced calcitonin gene-related peptide-containing vasodilator nerve function in mesenteric artery of spontaneously hypertensive rats

Effects of long-term treatment with angiotensin converting enzyme (ACE) inh ibitor on decreased function of calcitonin gene-related peptide (CGRP)-cont aining vasodilator nerves (CGRP nerves) in mesenteric resistance artery wer e investigated in spontaneously hypertensive rats (SHR). Eight-week-old SHR were treated for 7 weeks with 0.1% captopril, 0.01% temocapril, 0.05% pind olol or 0.005% hydralazine in drinking water. Long-term treatment with each drug significantly lowered mean blood pressure of SHR. In isolated and per fused mesenteric vascular beds with active tone, periarterial nerve stimula tion (PNS) (0.5 to 8 Hz) produced frequency-dependent vasodilations, which were abolished by CGRP(8-37) (CGRP-receptor antagonist) and significantly s maller in SHR than in normotensive Wistar Kyoto rats. Treatment of SHR with captopril and temocapril but not with pindolol and hydralazine resulted in significantly greater PNS-induced vasodilation than in non-treated SHR, bu t ACE-inhibitor treatment did not affect vasodilation induced by exogenous CGRP. In captopril-treated SHR preparations, PNS evoked significantly large r CGRP-like immunoreactive release than in non-treated SHR. In non-treated 15-week-old SHR preparations, direct perfusion of captopril or temocapril ( 0.1 mu M and 1 mu M) did not modify frequency-dependent vasodilation in res ponse to PNS. These results suggest that long-term ACE inhibitor treatment prevents or restores CGRP nerve function reduction in SHR.