Renal alpha-adrenergic receptor abnormality in the spontaneously hypertensive rat

R. M. Graham, W. A. Pettinger, Arthur I Sagalowsky, J. Brabson, T. Gandler

Research output: Contribution to journalArticlepeer-review

52 Scopus citations

Abstract

Activation of renal a-adrenergic receptors induces vasoconstriction, proximal tubular reabsorption of sodium, and inhibition of renin release. Excesses of these effects are present in varying degrees in animal models of, and in patients with, "essential" hypertension. Since essential hypertension is genetically determined, we sought abnormalities of renal α-adrenergic receptors in the Okamoto- Aoki strain of spontaneously hypertensive rats (sr-SHR) and their stroke-prone variant (sp- SHR). Total a-adrenergic receptor concentrations were determined by Scatchard analysis of [3H]dihydroergocryptine binding to a renal membrane fraction and were found to be increased (p < 0.02) in male sr-SHR at 4, 16, and 32 weeks of age and in female sr-SHR at 16 weeks of age as compared to age- and sex-matched Wistar-Kyoto controls. They were also increased in 9-week-old sp- SHR renal membranes (p < 0.005). Further studies revealed that this increase in renal a-adrenergic receptors was due entirely to an increase in α2-receptors as measured by [3H]yohimbine binding rather than to an increase in α,-receptors as quantitated by [3H]prazosin binding. No difference in binding affinities of the various radioligands could be demonstrated between any of the hypertensive and normotensive groups of rats. Plasma norepinephrine levels were elevated (p < 0.01) in the 4-, 9- and 16-week-old SHR, but not in the 32-week-old hypertensive rats. Thus, high renal α-adrenergic receptor number is coupled with a significant increase in plasma norepinephrine concentrations during the development of hypertension in SHR, By mediating an enhanced receptor-coupled response, such as increased proximal tubular sodium reabsorption, this abnormality of renal α-adrenergic receptors may contribute to some or all of the pathophysiologic derangements leading to hypertension in SHR.

Original languageEnglish (US)
Pages (from-to)881-887
Number of pages7
JournalHypertension
Volume4
Issue number6
DOIs
StatePublished - 1982

Keywords

  • Hypertension
  • Radioligand
  • Renal
  • SHR
  • α-receptor

ASJC Scopus subject areas

  • Internal Medicine

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