Sympathoinhibitory and depressor responses to long-term infusion of nifedipine in spontaneously hypertensive rats on high-salt diet

Short-term (by hour) intracerebroventricular (i.c.v.) or i.v. infusion of n ifedipine at low rates evokes parallel decreases in renal sympathetic nerve activity (RSNA) and blood pressure (BP) in spontaneously hypertensive rats (SHR). In the present study, effects of long-term administration of nifedi pine on BP and control of sympathetic tone were examined in SHR on a high-s alt (8%) diet. From 6 to 8 weeks of age, for 2 weeks concomitant with takin g a high-salt diet, rats were also treated with subcutaneous infusion of ni fedipine at 10, 50, or 100 mug/kg/h or vehicle solvent as control using osm otic minipumps. At the end of the 2-week treatment period, mean arterial pr essure (MAP), heart rate (HR), and RSNA at rest and in response to air-jet stress, i.c.v. injection of the alpha -adrenoceptor agonist guanabenz (25 m ug), and i.v. injection of the ganglionic blocker hexamethonium were record ed in conscious rats. In rats on nifedipine 50 or 100 mug/kg/h, resting MAP was significantly lower (136 +/- 4 or 130 +/- 4 vs. 145 +/- 2 mm Hg in con trol rats, p < 0.05 for both), the sympathoinhibitory and depressor respons es to i.c.v. guanabenz were significantly decreased, and the absolute decre ases in MAP in response to i.v. injection of hexamethonium were significant ly smaller. Sympathoexcitatory and presser responses to air-jet stress, how ever, were not affected by nifedipine. Infusion of nifedipine at the three rates for 2 weeks caused concentrations of plasma nifedipine in a dose-rela ted manner. Nifedipine was not detected in tissues of rats treated with 10 <mu>g/kg/h nifedipine but was present in brain and other tissues of rats tr eated with nifedipine at the two higher rates. Thus in SHR on high-salt int ake long-term treatment with nifedipine at 50 or 100 mug/kg/h decreased res ting BP and the sympathetic component in BP control. In addition to possibl e peripheral effects, long-term administration of nifedipine may also act c entrally to decrease sympathetic activity and BP, likely by increasing acti vity in central pathways involving sympathoinhibition, but not in pathways involving sympathoexcitation as evaluated by air-stress.