Effects of chronic administration of antihypertensive drugs on vasodilation mediated by calcitonin gene-related peptide-containing vasodilator nerves in spontaneously hypertensive rats.

Abstract

1. The effects of chronic administration of antihypertensive drugs on the vasodilator response mediated by calcitonin gene-related peptide (CGRP)-containing nerves were investigated in spontaneously hypertensive rats (SHR). 2. A 7 week period of antihypertensive treatment with captopril, nicardipine or propranolol during the developmental phase (8-15 weeks of age) significantly lowered the mean blood pressure of SHR when compared with non-treated SHR. 3. The mesenteric vascular beds isolated from SHR, which were chronically administered with captopril, propranolol or nicardipine, were perfused with Krebs' solution containing 7 mumol/L methoxamine to produce active tone and 5 mumol/L guanethidine to block adrenergic neurotransmission. 4. In the mesenteric vascular bed with active tone, perivascular nerve stimulation (PNS; 0.5-8 Hz) caused a frequency-dependent vasodilator response that was abolished by 100 nmol/L tetrodotoxin (neurotoxin) or 1 mumol/L CGRP (8-37), a CGRP receptor antagonist. 5. CGRP-containing nerve-mediated vasodilator responses were significantly greater in captopril-treated SHR and significantly smaller in nicardipine-treated SHR than in non-treated SHR. There was no difference between the response between propranolol-treated SHR and non-treated SHR. 6. These results suggest that chronic treatment with captopril reverses the reduced neurogenic vasodilation mediated by CGRP-containing nerves in SHR.