In the same chronically-instrumented conscious Long Evans rats, we assessed regional haemodynamic responses to i.v. and i.a. injections of endothelin-1 (ET-1) and big endothelin-1 at doses of 0.05 (n = 4) and 0.5 nmol kg-1 (n = 7). 2. For ET-1, the cardiovascular effects (initial hypotension and tachycardia with transient hindquarters vasodilation, followed by hypertension, bradycardia and renal, mesenteric and hindquarters vasoconstrictions) of i.v. and i.a. injections were not different. 3. Similarly, for big ET-1, the cardiovascular effects (hypertension, bradycardia and renal, mesenteric, and hindquarters vasoconstrictions) of i.v. and i.a. injections were not different. 4. At a dose of 0.5 nmol kg-1, i.v. or i.a., the pressor effects of ET-1 and big ET-1 were not different(area under curve [AUCO-30m.), ET-1 i.v. = 786 +/- 115 mmHg min; ET-1 i.a. = 880 +/- 165 mmHg min;big ET-1 i.v. = 878 +/- 93 mmHg min; big ET-1 i.a. = 833 +/- 103 mmHg min); but ET-1 caused greater renal, and lesser hindquarters, vasoconstrictions than big ET-1 (renal ET-1 i.v., AOC = 1550 +/- 211%min; ET-1 i.a., AOC = 1746 +/- 139% min; big ET-1 i.v., AOC = 1097 +/- 128% min; big ET-1 i.a.,AOC = 1041 +/- 119% min; hindquarters, ET-1 i.v., AOC = 758 +/- 176% min; ET-1 i.a. AOC =787 +/- 184% min; big ET-1 i.v., AOC = 1270 +/- 88% min; big ET-1 i.a., AOC = 1173 +/- 77% min), while the mesenteric vasoconstrictor effects of both peptides were not significantly different (ET-1 i.v.AOC = 1419 +/- 132% min; ET-l i.a., AOC = 1526 +/- 172% min; big ET-1 i.v., AOC = 1099 +/- 166%min; big ET-1 i.a., AOC = 1155 +/- 120% min).5. Under the conditions of our experiments, pulmonary clearance of ET-1, or pulmonary activation of big ET-1, was not apparent from the haemodynamic responses to i.v. and i.a. administration of the peptides. The results are consistent with previous findings indicating that local, rather than systemic,conversion of exogenous big ET-1 to ET-1 is responsible for its regional haemodynamic actions.
