Effect of angiotensin II receptor antagonist and endothelin receptor antagonist on nitroglycerin tolerance in rats.
OBJECTIVE
To investigate whether angiotensin II receptor antagonist and endothelin receptor antagonist can improve the nitroglycerin (Nit) tolerance in vivo.


METHODS
Twenty-four rats were divided into 4 groups (n = 6, each): Control group, Nitroglycerin (Nit) group, Nit + bosentan group and Nit + losartan group. Nitroglycerin tolerance was induced by 2-day treatment of (10 mg x kg(-1) nitroglycerin patch(0.05 mg/h). Angiotensin receptor antagonist losartan(10 mg x kg(-1) x d(-1)) and endothelin receptor antagonist bosentan (100 mg x kg(-1) x d(-1)) were given by gavage for 2 days respectively.


RESULTS
The least hypotensive response to sodium nitroprusside (SNP) was observed in Nit group. The effective percentages of hypotensive response to SNP were increased in both Nit + losartan group and Nit + bosentan group compared with Nit group [(31.95 +/- 4.45) % vs (21.00 +/- 3.69) %, P < 0.01 and (33.18 +/- 6.16) % vs (21.00 +/- 3.69) %, P < 0.01, respectively]. The maximal vessel relaxation induced by SNP was the same in 4 different groups but the highest EC50 (concentration which produces 50% of the maximal response to SNP) was found in tolerant group[(34 +/- 10) nmol/L, P < 0.01]. The ET-1 amounts in plasma and vascular tissue were markedly increased by 54% and 60% in Nit group compared with those in control group( P < 0.01). The ET-1 amounts in plasma and vascular tissue were decreased by 30% and 37% in Nit + losartan group compared with those in Nit group (P < 0.01).


CONCLUSIONS
Endothelin receptor antagonist and angiotensin II receptor antagonist could prevent against the Nit tolerance.
Zhang
J
J
Department of Pediatrics, First Hospital of Peking University, Beijing 100034.
Chen
Y
Y
Wang
X
X
Tang
T
T
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D000077300:Bosentan; D004361:Drug Tolerance; D065128:Endothelin Receptor Antagonists; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D005996:Nitroglycerin / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013449:Sulfonamides / Q000494:pharmacology*; D014665:Vasodilator Agents / Q000494:pharmacology
D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D065128:Endothelin Receptor Antagonists; D013449:Sulfonamides; D014665:Vasodilator Agents; D005996:Nitroglycerin; D019808:Losartan; D000077300:Bosentan