The altered balance between sympathetic nervous system and nitric oxide in salt hypertensive Dahl rats: ontogenetic and F2 hybrid studies

Abstract

Objective: We have demonstrated earlier that the nitric oxide (NO) system is not able to counterbalance effectively the hyperactivity of the sympathetic nervous system (SNS) in salt hypertension of young Dahl rats in which augmented superoxide anion formation lowers NO bioavailability. The aim of the present study was to determine whether SNS hyperactivity and/or relative NO deficiency are also present in salt hypertension elicited in adult Dahl rats, and whether they are associated with blood pressure (BP) in the F2 population of Dahl rats.

Design and methods: The contribution of major vasoactive systems [renin-angiotensin system (RAS), SNS and NO] and superoxide anions to BP maintenance was studied in SS/Jr rats in which salt hypertension was induced either in adulthood or in youth (8% NaCl diet from the age of 12 or 4 weeks). The contribution of particular vasoactive systems was also investigated in 122 young salt-loaded F2hybrids [derived from salt-sensitive (SS/Jr) and salt-resistant (SR/Jr) Dahl rats] which were fed a high-salt diet (8% NaCl) for 6 weeks after weaning. Mean arterial pressure (MAP) was measured in conscious animals subjected to acute consecutive blockade of RAS (captopril 10 mg/kg i.v.), SNS (pentolinium 5 mg/kg i.v.) and NO synthase (l-NAME 30 mg/kg i.v.).

Results: Dahl rats with salt hypertension induced in adulthood were also characterized by enhanced pentolinium-induced BP fall (DeltaMAPpento), but their residual BP (recorded after the blockade of both RAS and SNS) was unaltered, in contrast to its elevation seen in young salt-hypertensive rats. The BP rise after NO synthase inhibition by l-NAME (DeltaMAPL-NAME), which was substantially greater in adult than in young hypertensive rats, was not enhanced by superoxide scavenging with tempol in adult hypertensive animals, in which this drug elicited a moderate BP reduction only. Basal MAP of young salt-loaded F2 hybrids was positively associated not only with DeltaMAPpento (P < 0.0001) and residual BP (P < 0.001) but also with DeltaMAPL-NAME (P < 0.001). The slope of the relationship between basal BP and pentolinium-induced BP changes was steeper than that between basal BP and BP changes elicited by l-NAME. The positive correlation of basal BP with DeltaMAPpento/DeltaMAPL-NAME ratio (P < 0.01) indicates that an altered balance between sympathetic vasoconstriction and NO-dependent vasodilation was associated with high blood pressure, even in the F2 population of Dahl rats.

Conclusions: A comparison of young and adult salt-hypertensive Dahl rats stressed the importance of increased residual BP and relative NO deficiency for the severity of hypertension, because these two alterations were absent in a less-pronounced form of salt hypertension elicited in adulthood. The findings obtained in our young salt-loaded F2 population also confirm the major importance of both sympathetic hyperactivity and relative NO deficiency for the maintenance of salt hypertension in Dahl rats.