In this proposal emphasis is given the possible role of the electrogenic sodium-potassium pump in the genesis of experimental hypertension. It is now well established that the Na-K pump in blood vessels is in fact electrogenic. Studies in our laboratory indicate that the potassium ion is vasoactive by virtue of its effect on this pump, hyperkalemia dilating by stimulating the pump and hyperpolarizing the the membrane and hypokalemia constricting by suppressing the pump and depolarizing the membrane. Other studies in our laboratory suggest that the electrogenic pump is suppressed in experimental renal hypertension in dogs and rats and in essential hypertension in man. If so, this could in part explain the increase in total peripheral resistance. We propose to examine this hypothesis further by 1) examining the resistance response to hypokalemia and ouabain, 2) measuring tension responses of isolated arteries and veins to potassium and ouabain, 3) calculating active sodium pumping rate and membrane permeability in isolated arteries and veins from sodium 22 washout, membrane potential, and cell volume measurement, 4) measuring the membrane potential of the vascular smooth muscle cell in situ, and 5) measuring Na ion, K ion-ATPase and Ca ions-ATPase activity in red cell membranes and Na ion, K ion-ATPase activity of membranes from the vascular smooth muscle cell. All studies will be conducted in animals with spontaneous or experimental renal hypertension and in decreased active pumping, membrane potential and Na ion, K-ATPase activity would be compatible with the hypothesis. Another way a suppressed Na ion-K pump could contribute to the increased peipheral resistance is by """"""""waterlogging"""""""" the vessel. We therefore propose to measure vascular smooth muscle cell volume during prolonged suppression of the ouabain sensitive Na ion-K ion pump to see if in fact such suppression increases cell volume.

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National Heart, Lung, and Blood Institute (NHLBI)
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Experimental Cardiovascular Sciences Study Section (ECS)
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Pamnani, M B; Chen, S; Bryant, H J et al. (1991) Effects of three sodium-potassium adenosine triphosphatase inhibitors. Hypertension 18:316-24
Pamnani, M B; Bryant, H J; Clough, D L et al. (1991) Reversal of one-kidney, one-clip hypertension in rats. Effects on myocardial Na+, K(+)-ATPase, arterial Na(+)-K+ pump, arterial membrane potential, and plasma Na(+)-K+ pump inhibitory activity. Am J Hypertens 4:546S-555S
Pamnani, M B; Whitehorn, W V; Clough, D L et al. (1990) Effects of canrenone on blood pressure in rats with reduced renal mass. Am J Hypertens 3:188-95
Eliades, D; Swindall, B; Johnston, J et al. (1989) Effects of ANP on venous pressures and microvascular protein permeability in dog forelimb. Am J Physiol 257:H272-9
Pamnani, M B; Burris, J F; Jemionek, J F et al. (1989) Humoral Na+-K+ pump inhibitory activity in essential hypertension and in normotensive subjects after acute volume expansion. Am J Hypertens 2:524-31
Steffen, R P; O'Neill, J T; Haddy, F J (1988) Effect of theophylline on renal vasoactivity of acetate and adenosine. J Cardiovasc Pharmacol 11:682-6
Pamnani, M B; Bryant, H J; Whitehorn, W V et al. (1988) Sustained antihypertensive effect of chronic oral administration of 6-iodo-amiloride, a sodium channel blocker, in spontaneously hypertensive rats. J Hypertens Suppl 6:S678-80
Pamnani, M B; Mueller, G P; Ghai, R D et al. (1988) Role of atrial natriuretic factor in regulation of blood pressure in normotensive rats having reduced renal mass. Proc Soc Exp Biol Med 189:297-303
Pamnani, M B; Rinaudo, M S; Haddy, F J et al. (1988) Effect of 6-iodoamiloride in various models of experimental hypertension. Hypertension 11:445-51
Pamnani, M B; Bryant, H J; Haddy, F J (1987) Humoral sodium transport inhibitor in acute volume expansion and low renin hypertension. Hypertension 10:I78-83

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