As Urotensin II (UII) induced a transient pressor response in normotensive rats similar to the ‘escape phenomenon’ to aldosterone, we investigated if it activated the synthesis of renin and aldosterone.Design and method:
Sprague-Dawley normotensive rats were randomly divided into 4 groups. Group 1 received either a 7-days infusion of UII (600 pmol/kg/h) (cases) or a vehicle (controls). Group 2 underwent unilateral nephrectomy and a high sodium intake to antagonize the ‘escape phenomenon’. Group 3, besides unilateral nephrectomy and high sodium intake, received spironolactone, while Group 4 only received spironolactone. Blood pressure (BP) was continuously monitored by telemetry. Changes of genes and proteins expression of renin and Cyp11b2 were measured with Q-RT-PCR and immunohistochemistry, respectively.Results:
In Group 1, after a lag phase of 24–48 hours, UII transiently raised BP. In Group 2 it induced a progressive increase of BP over the week. In Group 3 and 4 spironolactone abolished both the early and the late pressor effects of UII.Results:
UII increased by 7-fold the expression of renin in the kidney of uninephrectomized rats (p < .01) in spite of salt-loading; it also increased Cyp11b2 gene and aldosterone synthase protein expression (p < .01) in the adrenocortical zona glomerulosa and prevented the salt-induced blunting of Cyp11b2 expression.Conclusions:
Thus, with normal sodium intake and excretory capabilities UII raised BP transiently; in salt-loaded uni-nephrectomized rats it raised BP progressively by counteracting the suppression of renin induced by salt loading. Overall these results suggest a role of UII enhanced renin and aldosterone synthesis in hypertension forms with impaired renal function.