Sympathoinhibition by central and peripheral infusion of nifedipine in spontaneously hypertensive rats

The present study assessed whether central mechanisms may contribute to the hypotensive effect of the calcium channel blocker nifedipine. In conscious , spontaneously hypertensive rats (SHR) on a high-salt diet, hemodynamic (m ean arterial pressure [MAP] and heart rate) and sympathetic (renal sympathe tic nerve activity) responses to low, central, intracerebroventricular infu sion rates (25 mu g . kg(-1) . (-1) for 2 hours) and peripheral intravenous rates (50 mu g . kg(-1) . h(-1) for 3 hours and then 100 mu g . kg(-1) . h (-1) for 2 hours) of nifedipine were evaluated. The distribution of nifedip ine in the blood and tissues was assessed at the end of the infusions. Nife dipine significantly inhibited renal sympathetic nerve activity and lowered MAP in SHR beginning 30 minutes after the start of the intracerebroventric ular infusion. The decrease of MAP by intravenous infusion began at 60 minu tes and was more profound with 100 mu g . kg(-1) . h(-1). Inhibition of sym pathetic activity preceded and then paralleled the decrease in blood pressu re; it occurred earlier with central (15 to 30 minutes) than with periphera l (30 to 60 minutes) infusion. Intravenous infusion resulted in concentrati ons of nifedipine in brain structures (brain stem, midbrain, and cortex) th at were 30% to 40% of those in the heart, kidneys, and liver. From the hemo dynamic and sympathetic responses and the distribution of nifedipine into t he central nervous system, we conclude that the peripheral infusion of nife dipine at relatively low rates may evoke a hypotensive response in SHR, not only via peripheral mechanisms, but also through central mechanisms, which will lead to an inhibition of sympathetic outflow and, therefore, a loweri ng of blood pressure.