Vasoactive systems in L-NAME hypertension: the role of inducible nitric oxide synthase.

OBJECTIVES: The contribution of the renin-angiotensin system (RAS) and the sympathetic nervous system (SNS) to blood pressure (BP) maintenance was evaluated in rats with N(omega)-nitro-L-arginine methyl ester (L-NAME) hypertension. Furthermore, we studied the extent of nitric oxide (NO) synthesis inhibition and the participation of remaining NO in the counterbalance of pressor systems, with a special reference to inducible nitric oxide synthase (iNOS).
METHODS: Wistar rats subjected to chronic L-NAME treatment (40 mg/kg per day for 4 weeks) were used. A consecutive blockade of RAS (captopril) and SNS (pentolinium) was followed by acute L-NAME injection. Dimethylguanidine or aminoguanidine were used to affect NO synthesis by iNOS.
RESULTS: L-NAME hypertensive rats had borderline augmentation of depressor response to captopril injection, but their BP fall after pentolinium was considerably enhanced compared with controls. Residual BP (recorded after simultaneous blockade of the RAS and the SNS) was elevated by 20-40% in hypertensive rats. Pronounced inhibition of NO synthase activity (50% reduction in the aorta and myocardium) was detected in L-NAME hypertensive rats in which the BP rise elicited by acute L-NAME injection was considerably attenuated (by 60-80%). In contrast, acute administration of dimethylguanidine [mixed endothelial NO synthase (eNOS)/iNOS inhibitor] to hypertensive rats induced a major BP rise similar to that caused by L-NAME injection in controls. Aminoguanidine (a selective iNOS inhibitor) caused a substantial BP rise in L-NAME hypertensive rats only.
CONCLUSION: The contribution of SNS to BP maintenance in L-NAME hypertension is more important than that of RAS. In L-NAME hypertensive rats the iNOS becomes a major source of hemodynamically important NO production, which is still insufficient to compensate prevailing vasoconstriction.