Nitric Oxide-Dependent Vasodilation in Young Spontaneously Hypertensive Rats

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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 pressor response to NO synthesis inhibition by NG-monomethyl-L-arginine (L-NMMA) in 9 conscious, chronically instrumented spontaneously hypertensive rats (SHR) at 12 weeks of age, ie, during the early established hypertensive stage. Nine age-matched Wistar-Kyoto rats (WKY) were used as controls. The pressor responses to L-NMMA (100 mg [middle dot] kg-1 IV bolus plus 1.5 mg [middle dot] kg-1 [middle dot] min-1 infusion for 60 minutes) as well as to non-NO-dependent pressor stimuli, namely, vasopressin (2, 4, and 8 ng [middle dot] kg-1) and phenylephrine (0.5, 1, and 2 [micro sign]g [middle dot] kg-1) given as IV boluses, were assessed both under control conditions and during suppression of autonomic reflexes by hexamethonium (30 mg [middle dot] kg-1 IV bolus + 1.5 mg [middle dot] kg (-1) [middle dot] min-1 infusion). Rather than being reduced, the pressor responses to L-NMMA were 39% and 71% larger in the control and areflexic conditions, respectively, than those observed in WKY (both P<0.01). A similar pattern was observed for the pressor responses to vasopressin (+37% and +68% in the control and areflexic conditions, respectively; both P<0.01) and phenylephrine, (+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 pressor responses to L-NMMA were similar in each strain, as were the pressor responses to vasopressin 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 prehypertensive as well as the early established hypertensive stage, NO-dependent vasodilation is preserved (if not enhanced) so that a putative impairment of this function provides no significant pathogenic contribution to the onset of hypertension in this experimental model. (Hypertension. 1998;32:735-739.)

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