| Research Abstract |
We have previously demonstrated innervation of calcitonin gene-related peptide (CGRP) containing vasodilator nerves (CGRP nerves) in the rat mesenteric artery and age-related decrease in CGRP nerve function in spontaneously hypertensive rats (SHR). The present study investigated the effects of long-term treatment with various antihypertensive drugs including angiotensin converting enzyme (ACE) inhibitors (captopril, temocapril), angiotensin 11 receptor (AT1-R) (TCV-116) antagonist, calcium (Ca) antagonist (amlodipine, nicardipine) , hydralazine on periarterial nerve function (adrenergic and CGRP nerves) in mesenteric resistance blood vessels of SHR.8-week old SHR were treated for 7 weeks with 0.1% captopril, 0.01% temocapril, 0.005% TCV-116, 0.01% amlodipine, 0.1% nicardipine or 0.005% hydralazine in drinking water. Isolated mesenteric vascular beds were perfused and perfusion pressure measured. In the preparation with resting tension, periarterial nerve stimulation (PNS ; 4, 8, 12 Hz)
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caused vasoconstriction induced by adrenergic stimulation. In precontracted preparations, PNS (0.5 to 8 Hz) produced frequency-dependent vasodilations, which were abolished by CGRP receptor antagonist (CGRP8-37) and significantly smaller in SHR than in normotensive Wistar Kyoto rats (WKY). In SHR CGRPmRNA level was significantly smaller than in WKY.Long-term treatment of SHR with each antihypertensive drug lowered systemic blood pressure. The treatment with captopril, temocapril, TCV-116, amlodipine but not with hydralazine resulted in significantly smaller PNS-induced vasoconstriction, and ACE inhibitor and TCV-l 16 treatment caused greater PNS-induced vasodilation than in non-treated SHR.However, direct perfusion of ACE inhibitors and AT1-R antagonist did not affect the PNS-induced vasoconstrictor and vasodilation. In ACE inhibitor-treated SHR preparations, PNS evoked significantly larger CGRP-like immunoreactive release than in non-treated SHR.The Ca antagonist, amlodipine inhibited the PNS-induced noradrenaline release but nicardipine increased the release. These results suggest that ACE inhibitors and AT1-R antagonist prevent or reverse CGRP nerve function reduction in SHR.The Ca antagonist inhibit adrenergic nerve function without affecting CGRP nerve function in SHR. Less
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