Maturation-Related Changes in Dopamine-Induced Relaxation of Isolated Rabbit Pulmonary Artery

Abstract

ABSTRACT. Studies were performed on isolated pulmonary arterial segments to investigate dopamine receptormediated relaxant effects at different times during development. Dopamine receptor-mediated relaxant effects can only be observed when vessels are precontracted with prostaglandin Fz, and in the presence of al, ag P, and serotonergic blockade. Helical strips of pulmonary arteries from rabbits of different ages (2, 7, 14, 30, and 90 days), partially precontracted by prostaglandin Fz, were tested for their responses to dopamine in the presence of prazosin M), yohimbin M), propranolol M), and methysergide M). Strips from 2-and 7-day-old rabbits were not induced to relax by dopamine, whereas those from 14-, 30-, and 90-day-old animals, after cumulative application of dopamine, underwent concentration-dependent relaxation. Dopamine (half the maximum response) concentration decreased during the development of rabbits from 14 to 90 days old. Mean values for apparent dopamine ED50 (half the maximum response) concentrations in the arteries of 14-, 30-, and 90-day old animals were 4.94 + 0.40, 2.02 + 0.30, and 0.113 + 0.028 wM, respectively.The effects of various dopamine antagonists on dopamineinduced relaxation were not markedly different at different ages. These findings indicate that dopamine receptor function is not fully developed in the pulmonary arteries of newborn rabbits, but matures as the age of the rabbit increases. (Pediatr Res 24: 160-165, 1988) Abbreviations ED50 concentration, concentration that produced half the maximum response pAz value, the negative logarithm of the molar concentration of the antagonist that produces a 2-fold shift to the right of the dose-response curve for the agonist Dopamine stimulates PI-adrenergic receptors causing positive inotropy and has been used to treat shock and congestive heart failure. In high doses, it also stimulates al-adrenergic receptors causing vasoconstriction. In low doses, however, specific dopaminergic receptors mediate vasodilation.In the cardiovascular system specific dopaminergic receptors are found in renal, mesenteric, splenic, coronary, cerebral, and femoral arteries. A vascular dopaminergic receptor classification has been proposed by Goldberg and Kohli (1, 2), in which the DA, receptor subserves smooth muscle relaxation, and the DA2 Received December 29, 1987; accepted March 18, 1988. Correspondence Dr. Miyako Mori, Department of Anesthesiology, Kobe University School of Medicine, Kusunoki-cho-7, Chuo-ku, Kobe, 650 Japan.Supported by grants from the Ministry of Education, Japan.receptor subserves the inhibition of noradrenaline release from postganglionic sympathetic nerves. Previously, we confirmed the existence of DAI dopamine receptors in the adult rabbit pulmonary artery (3). Dopamine produced a concentration-dependent relaxation of arterial strips contracted with prostaglandin F2, in the presence of prazosin (al-blocker), yohimbin (a2-blocker), propranolol (P-blocker), and methysergide (serotonin-blocker). The pulmonary circulatory system un...

Effects of catecholamines on the pulmonary circulation in the ovine fetus

“…Dopamine stimulates specific dopamine receptors at low concentration causing vasodilation, ␤ 1 -adrenoceptors at medium concentration, and ␣ 1 -adrenoceptors at high concentration (12). Evidence demonstrates that dopamine receptor activation may induce pulmonary vascular relaxation in various experimental models (23,29,30). However, our study fails to demonstrate any vasorelaxant effect at low-dose dopamine infusion in fetal pulmonary circulation.…”

“…Thus the vascular response to norepinephrine may depend on the ratio of ␣ 1 -to ␣ 2 -and ␤-adrenoceptors at the surface of the endothelium or of the smooth muscle cells (40). Maturational change in pulmonary arterial adre-noceptors previously described may explain conflicting results regarding the vascular response to norepinephrine (3,23,30).…”

In Vitro Effects Of Dopamine On Internal Thoracic Artery Graft Which Is Used In Coronary Artery Bypasses

“…Radioligand binding and light microscopy techniques showed the existence of D 1 and D 2 receptors on the rabbit pulmonary artery [17] and only D 1 receptors rat renal artery. [18] As well, Mori et al [19] have been observed D 1 related vasodilation on rabbit pulmonary artery, which is reduced by cis-flupenthixol (nonselective D 1 receptor blocker) in an organ bath study. It was suggested that vascular effects of dopamine are produced by specific dopamine receptors in cardiovascular system.…”

“…D 1 receptors had also been detected in rabbit pulmonary artery. [19] Katai et al [25] have been reported that SCH 23390, a DA 1 receptor antagonist, decreased dopamine related vasodilation on ITA in an in-vitro study. In addition to, there are some studies reported that dopamine causes vasoconstriction on ITA.…”

“…Thus, stimulation of these receptors determines the response of ITA to dopamine. [19,24,36] Dopamine produces a vasodilator response at the lower concentrations and therefore, dopamine is used commonly as renoprotective agent. However, Türkay et al reported that dopamine given at renal doses dose not protect renal tubular function in patients with normal heart and kidney functions undergoing coronary surgery and they do not recommend the use of dopamine for routine renal prophlaxis in this patients.…”