This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Murzenok, P. P. Articles by Leenen, F. H. H. Search for Related Content PubMed PubMed Citation Articles by Murzenok, P. P. Articles by Leenen, F. H. H. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information High Blood Pressure Related Collections Cardiovascular Pharmacology Other hypertension Hypertension - basic studies Autonomic, reflex, and neurohumoral control of circulation

(Hypertension. 2000;35:631.)
© 2000 American Heart Association, Inc.

Scientific Contributions

Sympathoinhibition by Central and Peripheral Infusion of Nifedipine in Spontaneously Hypertensive Rats

Piotr P. Murzenok; Bing S. Huang; Frans H. H. Leenen

From the University of Ottawa Heart Institute, Ontario, Canada.

Correspondence to Frans H.H. Leenen, MD, PhD, FRCPC, Hypertension Unit, H360, University of Ottawa Heart Institute, 40 Ruskin St, Ottawa, Ontario, Canada K1Y 4W7. E-mail fleenen{at}ottawaheart.ca

Abstract—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 µg · kg^-1 · h^-1 for 2 hours) and peripheral intravenous rates (50 µg · kg^-1 · h^-1 for 3 hours and then 100 µg · 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 µg · 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.

Key Words: nifedipine • infusion, intravenous • rats, inbred SHR • sympathetic nervous system • hemodynamics • pharmacokinetics

This article has been cited by other articles:

				J. A Staessen, J.-G. Wang, and W. H Birkenhager Outcome beyond blood pressure control? Eur. Heart J., March 2, 2003; 24(6): 504 - 514. [Full Text] [PDF]

				F. Forette, M.-L. Seux, J. A. Staessen, L. Thijs, M.-R. Babarskiene, S. Babeanu, A. Bossini, R. Fagard, B. Gil-Extremera, T. Laks, et al. The Prevention of Dementia With Antihypertensive Treatment: New Evidence From the Systolic Hypertension in Europe (Syst-Eur) Study Arch Intern Med, October 14, 2002; 162(18): 2046 - 2052. [Abstract] [Full Text] [PDF]