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

OBJECTIVEThe 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 METHODSWe 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 (N-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. RESULTSCompared 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. CONCLUSIONSThe 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.