Relative deficiency of nitric oxide-dependent vasodilation in salt-hypertensive Dahl rats: the possible role of superoxide anions.

OBJECTIVE: The contribution of major vasoactive systems (renin-angiotensin system, sympathetic nervous system and nitric oxide) to blood pressure maintenance and the possible involvement of superoxide anions in the reduced efficiency of nitric oxide (NO)-dependent vasodilation to counterbalance sympathetic vasoconstriction were studied in salt-hypertensive Dahl rats. DESIGN AND METHODS: We used Dahl salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) female rats kept on a low-salt (0.3% NaCl) or high-salt diet (8% NaCl) for 6 weeks since weaning. Mean arterial pressure (MAP) was measured in conscious animals subjected to acute consecutive blockade of the renin-angiotensin system (RAS) [captopril, 10 mg/kg intravenously (i.v.)], the sympathetic nervous system (SNS) (pentolinium, 5 mg/kg i.v.) and NO synthase (Nomega-nitro-L-arginine methyl ester (L-NAME), 30 mg/kg i.v.). Before the consecutive blockade of vasoactive systems one-half of the animals in each experimental group was pre-treated with a stable membrane-permeable mimetic of superoxide dismutase (tempol, 25 mg/kg i.v.) which functions as a superoxide scavenger.
RESULTS: Compared to normotensive SR/Jr animals, salt-hypertensive SS/Jr rats were characterized by an enhanced blood pressure (BP) fall after ganglionic blockade (-104 +/- 8 versus -62 +/- 5 mm Hg, P < 0.001) and by higher residual blood pressure recorded after the blockade of both RAS and SNS (70 +/- 3 versus 43 +/- 3 mmHg, P < 0.01), but there was only a borderline elevation of their BP response to acute NO synthase inhibition (67 +/- 6 versus 49 +/- 4 mmHg, P < 0.05). The acute tempol pre-treatment elicited the most pronounced reduction of basal BP (-13 +/- 1 mmHg, P < 0.001) in the salt-hypertensive SS/Jr group in which the BP rise after L-NAME administration was augmented by about 50%. On the contrary, tempol pre-treatment did not affect norepinephrine- or angiotensin II-dependent vasoconstriction.
CONCLUSIONS: The NO system is not able to counterbalance effectively the hyperactivity of the sympathetic nervous system in salt-hypertensive Dahl rats. The predominance of sympathetic vasoconstriction over NO-dependent vasodilation could be explained partially by enhanced NO inactivation due to augmented superoxide anion formation in hypertensive animals.