bq-123 and Renal-Insufficiency

Ischemia and subsequent reperfusion are known to impair renal function. We examined several agents that might prevent renal impairment or enhance the recovery of renal function after ischemia/reperfusion injury in rats. Different degrees of preventive effects were observed in rats treated with captopril, BQ-123 (endothelin type A receptor antagonist), sodium nitroprusside (SNP, a nitric oxide donor), and losartan (angiotensin II type 1 receptor antagonist). Only minimal changes in renal morphology were observed after treatment with losartan, SNP, captopril, and BQ-123 compared with control animals. On the other hand, lesions were prominent in the N(G)-nitro-L-arginine-methyl ester (L-NAME)- and L-arginine-treated rats. The Na(+)-K(+) ATPase activity of ischemic kidneys was, however, preserved in all treatment groups, except in those treated with L-arginine and L-NAME, which showed a marked reduction in Na(+)-K(+) ATPase activity. Our post-treatment data suggest that losartan and SNP have the greatest potential for therapeutic use to mitigate post-ischemic renal damage and functional impairment.

Topics: Adenosine Triphosphatases; Angiotensin II; Angiotensin II Type 1 Receptor Blockers; Animals; Arginine; Captopril; Ischemia; Kidney; Losartan; Male; NG-Nitroarginine Methyl Ester; Nitric Oxide Donors; Nitroprusside; Peptides, Cyclic; Rats, Wistar; Renal Insufficiency; Reperfusion; Reperfusion Injury

Bosentan is a nonspecific antagonist for endothelin (ET) receptors, and BQ123 is a specific inhibitor for ET-A receptors. We compared the effects of bosentan (10 mg/kg intravenously, i.v.) and BQ123 (10 mg/kg/h i.v.) on blood pressure and renal function in deoxycorticosterone acetate (DOCA)-salt rats, Dahl salt-sensitive (Dahl-S) rats, and normotensive Wistar rats. In normotensive Wistar rats, bosentan and BQ123 decreased blood pressure. Only BQ123 decreased glomerular filtration rate (GFR) and filtration fraction. These results indicate that ET-A receptors play a role in glomerular function. In DOCA-salt rats, bosentan and BQ123 caused a decrease in blood pressure to normal range and a decrease in renal vascular resistances. Bosentan decreased filtration fraction. Paradoxically, BQ123 caused a decrease in GFR. In Dahl-S rats, bosentan and BQ123 decreased blood pressure, but blood pressure did not reach normal ranges. Bosentan did not modify renal function, but BQ123 caused a decrease in the GFR and filtration fraction. Our results confirm the importance of specific and nonspecific ET antagonists in decreasing blood pressure in models of salt-dependent hypertension. However nonspecific inhibition of ET action did not improve renal function and specific inhibition of ET-A receptors by BQ123 temporarily worsened renal function.

Topics: Animals; Blood Pressure; Bosentan; Desoxycorticosterone; Endothelins; Glomerular Filtration Rate; Hypertension; Peptides, Cyclic; Rats; Rats, Wistar; Renal Circulation; Renal Insufficiency; Sodium Chloride; Sulfonamides