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 (mean arterial pressure [MAP] and heart rate) and sympathetic (renal sympathetic nerve activity) responses to low, central, intracerebroventricular infusion rates (25 microg. kg(-1). h(-1) for 2 hours) and peripheral intravenous rates (50 microg. kg(-1). h(-1) for 3 hours and then 100 microg. kg(-1). h(-1) for 2 hours) of nifedipine were evaluated. The distribution of nifedipine in the blood and tissues was assessed at the end of the infusions. Nifedipine significantly inhibited renal sympathetic nerve activity and lowered MAP in SHR beginning 30 minutes after the start of the intracerebroventricular infusion. The decrease of MAP by intravenous infusion began at 60 minutes and was more profound with 100 microg. kg(-1). h(-1). Inhibition of sympathetic activity preceded and then paralleled the decrease in blood pressure; it occurred earlier with central (15 to 30 minutes) than with peripheral (30 to 60 minutes) infusion. Intravenous infusion resulted in concentrations of nifedipine in brain structures (brain stem, midbrain, and cortex) that were 30% to 40% of those in the heart, kidneys, and liver. From the hemodynamic and sympathetic responses and the distribution of nifedipine into the central nervous system, we conclude that the peripheral infusion of nifedipine 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 lowering of blood pressure.
Murzenok
P P
PP
University of Ottawa Heart Institute, Ontario, Canada.
Huang
B S
BS
Leenen
F H
FH
D000311:Adrenal Glands / Q000378:metabolism; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D001933:Brain Stem / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000378:metabolism / Q000494:pharmacology*; D002540:Cerebral Cortex / Q000378:metabolism; D002552:Cerebral Ventricles / Q000187:drug effects; D004333:Drug Administration Routes; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007260:Infusion Pumps; D007262:Infusions, Intravenous; D007668:Kidney / Q000294:innervation / Q000378:metabolism; D008099:Liver / Q000378:metabolism; D008297:Male; D008636:Mesencephalon / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D009543:Nifedipine / Q000097:blood / Q000378:metabolism / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D013564:Sympathetic Nervous System / Q000187:drug effects* / Q000502:physiology; D014018:Tissue Distribution
D002121:Calcium Channel Blockers; D009543:Nifedipine