THE RESPONSE OF THE ISOLATED DUCTUS ARTERIOSUS TO TRANSMURAL STIMULATION AND DRUGS

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Abstract
1 Responses of isolated ductus arteriosus preparations from near term guinea-pigs and lambs to transmural electrical stimulation and drugs were studied in a low oxygen medium (Po2 19 to 28 mmHg). 2 Acetylcholine and noradrenaline contracted both vessels in a dose-dependent manner, their threshold being between 10−8 and 10−7 m. Transmural stimulation (pulse width 0.2 to 0.6 ms, typically 20 Hz) also contracted the vessels. 3 Atropine and phentolamine or dibenzyline selectively blocked responses to acetylcholine and noradrenaline, respectively. 4 In the guinea-pig ductus, part of the response to transmural stimulation was due to activation of intrinsic adrenergic nerves since the responses were reduced by α-adrenoceptor antagonists, bretylium or prior reserpine treatment, but not by atropine. The response of the lamb ductus to transmural stimulation varied greatly in magnitude and was inconsistently affected by α-adrenoceptor blocking drugs. 5 There was no evidence that transmural stimulation activated cholinergic nerves in either species. 6 After inactivation of α-adrenoceptors with dibenzyline, noradrenaline caused a β-adrenoceptor-mediated relaxation. Both this effect and isoprenaline-mediated relaxation were blocked by propranolol. β-Adrenoceptor activity was more prominent in the ductus of the guinea-pig than of the lamb. 7 Raising the Po2 from 19–28 to 92–98 mmHg increased the response of the guinea-pig ductus to transmural stimulation suggesting that, in this species, physiological elevation of oxygen tension at birth may increase transmitter release from intrinsic adrenergic nerves. Whether this mechanism would contribute to ductus closure remains an open question. 8 We postulate that β-adrenoceptor-mediated relaxation has a role in maintaining ductus patency in the guinea-pig foetus.