Low concentrations of angiotensin II unmask vasoconstrictory alpha 2-adrenoceptors in isolated perfused kidneys of spontaneously hypertensive rats.

OBJECTIVES

The aim of the present study was to evaluate the role of vascular alpha 1- and alpha 2-adrenoceptors in kidneys of spontaneously hypertensive rats (SHR) and normotensive Wistar Kyoto rats (WKY).

METHODS

SHR and WKY kidneys (12-14 weeks) were isolated and perfused with Krebs-Henseleit solution. Concentration-response curves for the alpha 1-adrenoceptor agonist methoxamine and the alpha 2-adrenoceptor agonist UK 14304 were constructed alone and in the presence of the alpha 1-adrenoceptor antagonist prazosin, the alpha 2-adrenoceptor antagonist idazoxan and exogenous angiotensin II.

RESULTS

Methoxamine induced a maximal pressor response of 247 +/- 9 mmHg with an EC50 of 1.3 +/- 0.1 microM in SHR and of 193 +/- 4 mmHg with an EC50 of 1.1 +/- 0.1 microM in WKY. The concentration-response curve for methoxamine was shifted to the right by prazosin with a pA2 value of 9.29 (SHR) and 9.26 (WKY) and by idazoxan with a pA2 value of 6.45 (SHR) and 6.33 (WKY). UK 14304 induced a maximal pressor response of 41 +/- 12 mmHg in SHR and of 37 +/- 8 mmHg in WKY. Angiotensin II (0.1 nM) did not significantly alter pressor responses to methoxamine but caused a marked shift to the left of the concentration-response curve for UK 14304. UK 14304 then induced a maximal pressor response of 92 +/- 13 mmHg with an EC50 of 0.07 +/- 0.01 microM in SHR and of 78 +/- 14 mmHg with an EC50 of 0.14 +/- 0.01 microM in WKY. In the presence of angiotensin II (0.1 nM) the concentration-response curve for UK 14304 was shifted to the right by prazosin with a pKB of 6.36 (SHR) and 6.33 (WKY) and by idazoxan with a pKB of 7.68 (SHR) and 7.65 (WKY).

CONCLUSIONS

The results demonstrate a predominant role of vasoconstrictory alpha 1-adrenoceptors over alpha 2-adrenoceptors in SHR and WKY isolated kidneys. Low physiological concentrations of angiotensin II unmask functional vascular alpha 2-adrenoceptors which are slightly more sensitive in SHR than in WKY kidneys.