| Budget Amount *help |
¥13,300,000 (Direct Cost: ¥13,300,000)
Fiscal Year 1999: ¥6,600,000 (Direct Cost: ¥6,600,000)
Fiscal Year 1998: ¥6,700,000 (Direct Cost: ¥6,700,000)
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| Research Abstract |
We have previously demonstrated innervation of calcitonin gene-related peptide (CGRF)-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 (enalapril, temocapril), angiotensin II receptor (AT1-R) (TCV-116) antagonist, calcium antagonist (amlodipine, pranidipine, nicardipine), hydralazine on periatrerial nerve function (adrenergic and CGRP nerves) in mesenteric resistance blood vessels of SHR. 8-week old SHR were treated for 7 weeks with 0.01% enalapril, 0.05% temocapril, 0.005% TCV-116, 0.01% amlodipine, 0.0035% pranidipine, 0.1% nicardipine or 0.005% hydralazine in drinking water or rat chew. Isolated mesenteric vascular beds were perfused and perfusion pressure measured. In the preparation with resting tension, periarte
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rial nerve stimulation (PN ; 4, 8, 12Hz) 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-116 treatment caused greater PNS-induced vasodilation than in non-treated SHR. In ACE inhibitor-treated SHR preparations, PNS evoked significantly larger CGRP-like immunoreactive release than in non-treated SHR. Amlodipine and pranidipine 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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