a1- and a2-Adrenoceptor Control of Sodium Transport Reverses in Developing Hypertension

a-Adrenergic receptor (AR) activation enhances sodium retention in certain forms of hypertension. The objective of the present study was to understand the role of a-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 a1-AR agonist phenylephrine increased Na uptake by 50% into DT cells of 6-week SHR; no effect was observed with WKY cells. The a2-AR agonist B-HT 933 increased uptake by only 10%. At 12 weeks, the pattern of a-AR regulation was reversed: a1-AR–induced sodium uptake was only 15%, whereas a2-AR activation increased sodium uptake by 35% in SHR and WKY cells. a1-AR–induced sodium uptake in 6-week SHR cells was abolished by prazosin; a2-AR–stimulated sodium uptake was blocked by yohimbine in 12-week SHR and WKY. Competitive binding studies were performed with [H]prazosin and a1A-, a1B-, and a1D-selective antagonists with DT cell membranes from 6and 12-week SHR and WKY. a2-AR subtypes were determined with [ H]rauwolscine and a2Aand a2B-selective antagonists. Expression of a1B-ARs was increased 4-fold in DT cells during the developing phase of hypertension in SHR. No change was detected in a2-AR expression. DT cells transiently increase [Ca ]i in response to a1-AR agonists from 6-week but not 12-week SHR. Conversely, a2-AR agonists increase [Ca ]i at 12 weeks. In summary, during developing hypertension, a1-ARs increase sodium uptake and [Ca]i in SHR cells. Expression of a1B-ARs is selectively upregulated during developing hypertension. In established hypertension (and normotension), a2-ARs regulate sodium transport and [Ca ]i in DT cells. We conclude that a molecular switch of a1-AR and a2-AR signaling occurs in DT cells during the development of hypertension. (Hypertension. 1999;33[part II]:524-529.)