Nisoldipine and pressure-natriuresis curves in transgenic (mRen2)27 rats

Abstract

The mechanism by which antihypertensive drugs influence pressure natriuresis gives insight into their mode of action. We tested the effects of nisoldipine on pressure natriuresis, glomerular filtration rate, and renal blood flow in transgenic (mRen2)27 rats and Sprague-Dawley Hannover control rats. The rats were anaesthetized, uninephrectomized with denervation of the remaining kidney, administered noradrenaline, 17-hydroxycorticosterone, vasopressin, and aldosterone to 'clamp' these regulatory systems and nisoldipine (0.5 mg/kg bolus plus 0.017 mg/kg per min). The glomerular filtration rate and renal plasma flow were measured with inulin and PAH. Renal perfusion pressure was varied from approximately 100 to approximately 200 mmHg with clamps above and below the kidney. Nisoldipine shifted not only the pressure-diuresis and pressure-natriuresis curves but also the fractional sodium and water curves leftwards in transgenic (mRen2)27 rats, but not in Sprague-Dawley Hannover rats. Nisoldipine increased the glomerular filtration rate and renal blood flow in transgenic (mRen2)27 rats but not in Sprague-Dawley Hannover rats. Nisoldipine shifts the pressure-natriuresis curve in transgenic (mRen2)27 rats leftwards; sodium and water excretion is increased for any given perfusion pressure. This effect is intrinsic to the kidney and is associated with inhibition of tubular sodium and water reabsorption and with an increase in renal perfusion.