SUMMARY The hemodynamic effect of moderate K+ depletion in hypertension is unknown. Since severe K+ depletion reduces systemic vascular resistance in normotensive rats, we determined the effect of K+ depletion on the natural history of hypertension in spontaneously hypertensive rats (SHR). Wistar-Kyoto rats (WKY) and SHR were fed a K + -replete, a moderately K + -depleted, or a severely K + -depleted diet. After 6 weeks, systemic vascular resistance was reduced by 25% in WKY on the severely K + -depleted diet while mean arterial pressure and systemic vascular resistance were comparable in WKY on the other two diets. In SHR on the severely K + -depleted diet for 6 weeks, muscle K+ was reduced by 23% and growth rate by 65%. In SHR on the moderately K + -depleted diet, growth rate was reduced by 23% after 3 weeks. By 6 weeks, however, muscle K + was reduced by 5 to 6% and growth rate was comparable to that in SHR receiving the K + -replete diet. The administration of either K + -depleted diet prevented the development of hypertension (systolic blood pressure: severely depleted, 116 ± 4; moderately depleted, 122 ± 3; K + -replete, 155 ± 5 nun Hg; p < 0.001 compared with both K + -depleted groups) and reversed established hypertension (systolic blood pressure: severely depleted, 116 ± 4; moderately depleted, 128 ± 3; K+-replete, 171 ± 5 mm Hg; p<0.001 compared with both K + -depleted groups). The protective effect of K + depletion was mediated by a 40% reduction in systemic vascular resistance. These results suggest that K + depletion has a potent antihypertensive effect in SHR. The vasodilative effect of moderate K+ depletion also appears to be specific for hypertension since it did not occur in normotensive WKY. (Hypertension 8: 990-996, 1986) KEY WORDS • hypokalemia * electrolytes • hemodynamics • angiotensin F OR many years sodium was the only electrolyte considered relevant to the control of blood pressure in patients with essential hypertension. While recent studies have demonstrated that other electrolytes such as calcium 1 and chloride 2 ' 3 may also be of importance in the pathogenesis of hypertension, there have been few experimental studies on the hemodynamic effects of potassium in hypertension. This paucity of information on potassium is surprising since potassium is the major intracellular cation and since many of the 30 million hypertensive patients in the United States are treated with diuretic agents and manifest mild hypokalemia and a decrease in total body potassium. Although there have been few studies on the effect of potassium in hypertensive animals, there have been hemodynamic studies on the effects of potassium in normotensive animals. Acute hypokalemia, as occurs when vessels or limbs from normokalemic animals are perfused with hypokalemic solutions, results in vasoconstriction.5 " 7 In contrast, chronic, severe total body potassium depletion induced by diet or dialysis, or both, results in a decrease in systemic vascular resistance (SVR) and mean arterial pressure (MAP).8 " 10 Unfortunat...