Alpha1- and alpha2-adrenoceptor control of sodium transport reverses in developing hypertension.

Abstract

Alpha-Adrenergic receptor (AR) activation enhances sodium retention in certain forms of hypertension. The objective of the present study was to understand the role of alpha-ARs in regulating sodium transport by distal tubules (DT). DT cells were isolated from kidneys of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at 6 weeks, when hypertension is developing, or at 12 weeks, when hypertension is established. The alpha1-AR agonist phenylephrine increased 22Na uptake by 50% into DT cells of 6-week SHR; no effect was observed with WKY cells. The alpha2-AR agonist B-HT 933 increased uptake by only 10%. At 12 weeks, the pattern of alpha-AR regulation was reversed: alpha1-AR-induced sodium uptake was only 15%, whereas alpha2-AR activation increased sodium uptake by 35% in SHR and WKY cells. alpha1-AR-induced sodium uptake in 6-week SHR cells was abolished by prazosin; alpha2-AR-stimulated sodium uptake was blocked by yohimbine in 12-week SHR and WKY. Competitive binding studies were performed with [3H]prazosin and alpha1A-, alpha1B-, and alpha1D-selective antagonists with DT cell membranes from 6- and 12-week SHR and WKY. alpha2-AR subtypes were determined with [3H]rauwolscine and alpha2A- and alpha2B-selective antagonists. Expression of alpha1B-ARs was increased 4-fold in DT cells during the developing phase of hypertension in SHR. No change was detected in alpha2-AR expression. DT cells transiently increase [Ca2+]i in response to alpha1-AR agonists from 6-week but not 12-week SHR. Conversely, alpha2-AR agonists increase [Ca2+]i at 12 weeks. In summary, during developing hypertension, alpha1-ARs increase sodium uptake and [Ca2+]i in SHR cells. Expression of alpha1B-ARs is selectively upregulated during developing hypertension. In established hypertension (and normotension), alpha2-ARs regulate sodium transport and [Ca2+]i in DT cells. We conclude that a molecular switch of alpha1-AR and alpha2-AR signaling occurs in DT cells during the development of hypertension.