This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Gesek, F. A. Search for Related Content PubMed PubMed Citation Articles by Gesek, F. A. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information High Blood Pressure Hazardous Substances DB PHENYLEPHRINE PRAZOSIN HYDROCHLORIDE SODIUM TRITIUM

(Hypertension. 1999;33:524-529.)
© 1999 American Heart Association, Inc.

Scientific Contributions

₁- and ₂-Adrenoceptor Control of Sodium Transport Reverses in Developing Hypertension

Frank A. Gesek

From the Pharmacology Department, Dartmouth Medical School, Hanover, NH.

Correspondence to Dr Frank A. Gesek, Pharmacology Department, Dartmouth Medical School, 7650 Remsen, Room 611, Hanover, NH 03755. E-mail fg{at}dartmouth.edu

Abstract—-Adrenergic receptor (AR) activation enhances sodium retention in certain forms of hypertension. The objective of the present study was to understand the role of -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 ₁-AR agonist phenylephrine increased ²²Na uptake by 50% into DT cells of 6-week SHR; no effect was observed with WKY cells. The ₂-AR agonist B-HT 933 increased uptake by only 10%. At 12 weeks, the pattern of -AR regulation was reversed: ₁-AR–induced sodium uptake was only 15%, whereas ₂-AR activation increased sodium uptake by 35% in SHR and WKY cells. ₁-AR–induced sodium uptake in 6-week SHR cells was abolished by prazosin; ₂-AR–stimulated sodium uptake was blocked by yohimbine in 12-week SHR and WKY. Competitive binding studies were performed with [³H]prazosin and _1A-, _1B-, and _1D-selective antagonists with DT cell membranes from 6- and 12-week SHR and WKY. ₂-AR subtypes were determined with [³H]rauwolscine and _2A- and _2B-selective antagonists. Expression of _1B-ARs was increased 4-fold in DT cells during the developing phase of hypertension in SHR. No change was detected in ₂-AR expression. DT cells transiently increase [Ca²⁺]_i in response to ₁-AR agonists from 6-week but not 12-week SHR. Conversely, ₂-AR agonists increase [Ca²⁺]_i at 12 weeks. In summary, during developing hypertension, ₁-ARs increase sodium uptake and [Ca²⁺]_i in SHR cells. Expression of _1B-ARs is selectively upregulated during developing hypertension. In established hypertension (and normotension), ₂-ARs regulate sodium transport and [Ca²⁺]_i in DT cells. We conclude that a molecular switch of ₁-AR and ₂-AR signaling occurs in DT cells during the development of hypertension.

Key Words: receptors, adrenergic • blood pressure • catecholamines • epinephrine • hypertension • calcium • norepinephrine

This article has been cited by other articles:

				K. DiPetrillo, B. Coutermarsh, and F. A. Gesek Urinary tumor necrosis factor contributes to sodium retention and renal hypertrophy during diabetes Am J Physiol Renal Physiol, January 1, 2003; 284(1): F113 - F121. [Abstract] [Full Text] [PDF]

				X. Jiao, P. J. Gonzalez-Cabrera, L. Xiao, M. E. Bradley, P. W. Abel, and W. B. Jeffries Tonic Inhibitory Role for cAMP in alpha 1a-Adrenergic Receptor Coupling to Extracellular Signal-Regulated Kinases 1/2 J. Pharmacol. Exp. Ther., October 1, 2002; 303(1): 247 - 256. [Abstract] [Full Text] [PDF]