DIMINISHED EXPRESSION OF RENAL DOPAMINE D1(A) RECEPTORS IN THE KIDNEYINNER MEDULLA OF THE SPONTANEOUSLY HYPERTENSIVE RAT

Background Dysfunctional dopamine neurotransmission and greater than n ormal retention of salt have been found for renal proximal tubules of the spontaneously hypertensive rat, Objective To determine whether the re are differences between kidney D1(A) dopamine receptor distribution s of spontaneously hypertensive rats and Wistar-Kyoto rats. Methods We examined the expression of D1(A) dopamine receptors in kidneys of spo ntaneously hypertensive rats and the normotensive Wistar-Kyoto rat thr ough Western blots and immunocytochemistry, using highly specific anti peptide antibodies directed against the receptor, Results The specific ity of the antisera was demonstrated by Western blot studies, using pr oximal tubules, from Wistar-Kyoto rats. The antiserum recognized a maj or polypeptide with M-r of 72 kDa and a minor protein of M-r 66 kDa, w hich were not detected either by antigen-adsorbed or by preimmune sera , In renal cortex of both Wistar-Kyoto rats and spontaneously hyperten sive rats, D1(A) receptors were expressed at equivalent levels. In the inner medulla of Wistar-Kyoto rat, there was diminished (by 60%) expr ession of D1(A) receptors compared with that of the renal cortex. Howe ver, the expression of D1(A) receptors in the inner medulla in the spo ntaneously hypertensive rat was even more diminished (by 83%) relative to levels found in spontaneously hypertensive rat renal cortex, Immun ocytochemical studies localized the D1(A) receptor protein in renal co rtex primarily to epithelia of tubules. Relative to renal cortex, ther e was an overall decrease in staining intensity in the inner medulla b oth of Wistar-Kyoto rats and of spontaneously hypertensive rats. Compa red with that of Wistar-Kyoto rat, the intensity of staining of D1(A) receptors in the inner medulla of spontaneously hypertensive rats was greatly diminished, confirming the Western blot analyses. The less tha n normal expression of D1(A) receptors in the inner medulla of spontan eously hypertensive rats might be of physiologic importance in the eti ology of greater than normal retention of salt and hypertension in spo ntaneously hypertensive rats. (C) 1998 Lippincott-Raven Publishers.