Mechanism of adrenal angiotensin II receptor changes after nephrectomy in rats

At 48 h after bilateral nephrectomy in rats there is a two- to threefold increase in the number of adrenal angiotensin II receptors and a decrease in Kd of smooth muscle angiotensin II receptors. These changes have been attributed to the absence of circulating angiotensin II. Serum K+, which increases after nephrectomy may be an important and overlooked modulator. Therefore, the present experiments were designed to assess the role of K+ as a regulator of angiotensin II receptors after nephrectomy. Serum K+ was controlled with Na polystyrene sulfonate (Kayexalate), a resin designed to exchange Na+ for K+ in the gastrointestinal tract. Acutely nephrectomized rats were divided into two groups: experimental animals received Kayexalate resin every 12 h for four doses, and controls received Kayexalate exchanged with KCl in vitro before gavage. There was a significant positive correlation serum K+ and aldosterone (r = 0.78, P less than 0.001). Kayexalate maintained a normal serum K+ of 5.9 +/- 0.2 meq/liter (n = 27), aldosterone 25 +/- 3 ng/dl (n = 27) and adrenal receptor concentration of 934 +/- 156 fmol/mg protein (n = 4). Control animals had significantly higher serum K+ of 10.5 +/- 0.4 meq/liter (n = 23), aldosterone 435 +/- 32 (n = 23), and adrenal receptors of 2726 +/- 235 fmol/mg protein (n = 4). There was a linear relationship between serum K+ and number of adrenal receptors (r = 0.87). No such relationship was present in uterine smooth muscle. Therefore, these studies demonstrate that K+ modulates the number of adrenal but not smooth muscle angiotensin II receptors after nephrectomy. This is the first evidence that potassium modulates angiotensin II receptors independently of changes in angiotensin II blood levels.