(Hypertension. 1997;29:1192-1198.)
© 1997 American Heart Association, Inc.
Articles |
Nifedipine Attenuates Systemic and Renal Vasoconstriction During Nitric Oxide Inhibition in Humans
From the Department of Nephrology and Hypertension, University Hospital Utrecht (Netherlands).
Correspondence to Lioe-Ting Dijkhorst-Oei, Department of Nephrology and Hypertension, University Hospital Utrecht, Room F03.226, PO Box 85500, 3508 GA Utrecht, Netherlands. E-mail t.j.rabelink{at}digd.azu.nl
Abstract Clinical states associated with nitric oxide deficiency are often accompanied by vasoconstriction. We studied the effects of prolonged infusion of the nitric oxide synthase inhibitor NG-monomethyl-L-arginine (L-NMMA) on systemic and renal hemodynamics in humans and the reversibility of the established vasoconstriction by calcium channel blockade with nifedipine. Seven healthy men underwent three 7-hour clearance studies. During one study, L-NMMA (3 mg/kg priming dose plus 3 mg·kg-1·h-1) was infused during hours 2 through 5, and during another study, nifedipine (0.015 mg/kg priming dose plus 0.015 mg·kg-1·h-1) was coinfused during hours 4 and 5. A third study served as time control. L-NMMA elicited reproducible systemic and renal vasoconstriction that was stable during the 4 hours of infusion. Systemic vascular resistance index, calculated from bioimpedance-derived cardiac index, increased from 22±1 to 29±2 mm Hg·min·m2·L-1 (P<.05). Mean arterial pressure rose by 4±1 mm Hg (P<.05), and heart rate, stroke index, and cardiac index decreased. Renal blood flow, calculated from renal plasma flow, decreased from 1182±101 to 785±53 mL/min, and renal vascular resistance increased from 73±5 to 115±6 mm Hg·min·L-1 (P<.05). Glomerular filtration rate decreased from 114±6 to 104±6 mL/min (P<.05), and filtration fraction increased. Sodium excretion fell from 89±9 to 32±7 µmol/min (P<.05). Nifedipine completely reversed systemic vasoconstriction. Nifedipine caused partial restoration of renal vascular resistance and complete normalization of glomerular filtration rate and sodium excretion but left the elevated filtration fraction unaltered. We conclude that sustained nitric oxide deficiency in humans is accompanied by strong systemic and renal vasoconstriction, decreased glomerular filtration rate, and sodium retention. Nifedipine can reverse most of these effects, suggesting a role for calcium channel blockade in pathological states of impaired nitric oxide activity.
Key Words: L-NMMA • blood pressure • glomerular filtration rate • calcium channel blockers
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