Responses of isolated rabbit thoracic aortae to endothelin-1 and several vasoactive substances a new blood perfusion circuit under the controlled conditions of resistance and flow

Abstract

Analysis of the reactivity of isolated rabbit thoracic aorta to isoproterenol and norepinephrine injected into a blood perfusion circuit intraarterially (i.a.) under controlled conditions of resistance and flow using conscious support rabbits revealed that with pressure loads of 10–20 mmHg for a vessel-holding chamber and 60 mmHg for a Starling pneumatic resistance set, a suitable vasodilation or vasoconstriction can be obtained. This leads us to assume that the system could be used to assess the direct influence of vasoactive substances on vasomotor tone and, furthermore, the support rabbit could be used for systemic hemodynamic variables and behavior observation. The i.a. injection of increasing doses of endothelin (ET) (0.01–0.3 μg) caused a weak but long-lasting and dose-dependent vasoconstriction of the thoracic aorta; its effect was less potent than that of angiotensin II or norepinephrine when their peak responses were compared. The duration of vasoconstriction caused by 0.3 μg i.a. of ET was ∼ 30 min and much longer than that of angiotensin II and norepinephrine. Histamine, serotonin, and prostaglandin E 2 produced noticeable dose-dependent vasoconstriction. When ET (0.1–3 μg) was injected i.v. to conscious rabbits, the systemic blood pressure, which first dropped and then rose, was accompanied by significant changes in the heart rate in a reciprocal way. The observed rise in the blood pressure with the accompanying decrease in the heart rate lasted for at least 30 min following 1 μg i.v. of ET. The maximal tolerable dose of ET in conscious rabbits was about 1 μg i.v. In summary, it may be concluded that ET is a long-acting vasoconstrictor and might be more capable of producing an effect downstream of its release site; however, it is very toxic in the rabbit.