Acute renal failure in 2K2C Goldblatt hypertensive rats during antihypertensive therapy: comparison of an angiotensin AT(1) receptor antagonist and clonidine analogues

1 This study compared the effect of a non-peptide angiotensin II receptor a ntagonist and a series of clonidine analogues on blood pressure and renal f unction in a two-kidney two-clip Goldblatt rat model of hypertension subjec ted to 2 weeks of dietary sodium deprivation. 2 Animals received either vehicle, the angiotensin II antagonist, ZD7155 or structural analogues derived from clonidine (AL-11, AL-12 and CN-10) at 10 mg kg(-1) day(-1) for 4 days. 3 All groups of rats had systolic blood pressure in the hypertensive range (160-180 mmHg). ZD7155 caused a 33-mmHg fall in blood pressure (P < 0.05) a nd raised plasma urea and creatinine four- to six-fold. 4 AL-12 decreased blood pressure by 30 mmHg (P < 0.05), but had no effect o n water intake, urine flow or plasma urea and creatinine. AL-11 and CN-10 h ad minimal effects on blood pressure and water intake and while CN-10 decre ased urine flow on the third treatment day, AL-11 markedly reduced urine fl ow by some 70%. 5 These data show that in this sodium deficient renovascular model of hyper tension, blockade of angiotensin II receptors normalizes blood pressure but causes renal failure, whereas the vasodepressor action of the clonidine an alogue AL-12 occurs without detriment to renal function. These findings imp ly that angiotensin II receptor antagonists could lead to renal failure if used as antihypertensive agents in renovascular hypertension whereas this w ould be avoided with the use of clonidine-like analogues.