NITRIC OXIDE-DEPENDENT VASODILATION IN YOUNG SPONTANEOUSLY HYPERTENSIVE RATS

Conflicting evidence exists on the possible impairment of tonic nitric oxide (NO)-mediated vasodilation as a causative factor in the genesis of human as well as experimental hypertension. We evaluated the tonic NO-dependent vasodilation from the presser response to NO synthesis i nhibition by N-G-monomethyl-L-arginine (L-NMMA) in 9 conscious, chroni cally instrumented spontaneously hypertensive rats (SHR) at 12 weeks o f age, ie, during the early established hypertensive stage. Nine age-m atched Wistar-Kyoto rats (WKY) were used as controls. The presser resp onses to L-NMMA (100 mg . kg(-1) IV bolus plus 1.5 mg . kg(-1) . min(- 1) infusion for 60 minutes) as well as to non-NO-dependent presser sti muli, namely, vasopressin (2, 4, and 8 ng . kg(-1)) and phenylephrine (0.5, 1, and 2 mu g . kg(-1)) given as IV boluses, were assessed both under control conditions and during suppression of autonomic reflexes by hexamethonium (30 mg . kg(-1) IV bolus+1.5 mg . kg(-1) min-L infusi on). Rather than being reduced, the presser responses to L-NMMA were 3 9% and 71% larger in the control and areflexic conditions, respectivel y, than those observed in WKY (both P<0.01). A similar pattern was obs erved for the presser responses to vasopressin (f37% and +68% in the c ontrol and areflexic conditions, respectively; both P<0.01) and phenyl ephrine, (+20% and +52%; both P<0.05). Additional groups of 6-week-old prehypertensive SHR (n=11) and age-matched WKY (n=11) were subjected to an identical protocol: in these animals, the presser responses to L -NMMA were similar in each strain, as were the presser responses to va sopressin and phenylephrine in both control and areflexic conditions. In conclusion, our observations indicate that during the developmental phase of hypertension in the SHR model, namely, during the prehyperte nsive as well as the early established hypertensive stage, NO-dependen t vasodilation is preserved (if not enhanced) so that a putative impai rment of this function provides no significant pathogenic contribution to the onset of hypertension in this experimental model.