Vasodilator effects of adrenomedullin on small pulmonary arteries and veins in anaesthetized cats

Abstract

1 This study was conducted to determine adrenomedullin (AM) action sites in the pulmonary vascular bed and the relation between its vasodilator e ects and vascular tone. Moreover, an examination was made into whether calcitonin gene-related peptide (CGRP) receptors mediate pulmonary vasodilatations induced by AM. To this end, we directly measured internal diameter (i.d.) changes in small pulmonary arteries and veins (100 ± 1100 mm i.d.) by use of an X-ray televison system on the in vivo cat lung. 2 Under control (resting vascular tone) conditions, AM injections into the left main pulmonary artery caused dose-related i.d. increases in both small arteries and veins. The mean i.d. increase of the 100 ± 1100 mm arteries (4+1, 11+2, and 17+2% with 0.01, 0.1, and 1 nmol kg 71 AM, respectively) was signi®cantly larger than that for the veins (1+1, 5+2, and 7+2% with 0.01, 0.1 and 1 nmol kg 71 AM, respectively) whatever the injected dose of AM. 3 When unilobar hypoxia (5% O 2 ) had decreased the i.d. of the 100 ± 1100 mm arteries and veins by 16+3 and 6+3%, respectively, AM (0.1 nmol kg 71 ) was able to induce signi®cantly larger i.d. increases in the arteries (28+3%) and veins (11+3%) than those under control conditions. 4 The AM-induced i.d. response pattern in the serially connected pulmonary arteries was quite di erent from that induced by CGRP; AM caused a greater increase in smaller vessels (100 ± 500 mm) than in larger vessels (500 ± 1100 mm). In the case of CGRP, a greater increase was observed in the larger vessels. 5 CGRP 8 ± 37 (100 nmol kg 71 , i.v., followed by a continuous infusion of 0.2 nmol kg 71 min 71 ) had no signi®cant e ect on the i.d. increase induced by AM (0.1 nmol kg 71 ) in any serial segments of the arteries and veins. 6 The results indicate that, in the cat, AM induces greater vasodilatation in small pulmonary arteries and lesser vasodilatation in small veins, the maximum dilatation being in the more peripheral arterial segment (100 ± 500 mm). The vasodilator e ect of AM was enhanced when vascular tone was elevated. The data suggest that the AM-induced pulmonary vasodilatation is not mediated by CGRP receptors but by its own speci®c receptor.

Pulmonary Vasodilator Response to Adrenomedullin in Patients with Pulmonary Hypertension

“…Experimental studies have shown that intralobar arterial infusion of AM causes a dose-related decreases in pulmonary vascular resistance under conditions of high pulmonary vascular tone (7-9). Shirai et al have shown that AM dilates small pulmonary arteries in cats (100-500 µm), which are the main site of hypoxic pulmonary vasoconstriction (27). In the present study, intravenous infusion of AM significantly decreased pulmonary vascular resistance in patients with primary pulmonary hypertension.…”

Adrenomedullin influences magnocellular and parvocellular neurons of paraventricular nucleus via separate mechanisms

“…Initial studies showed that intravenous infusion of AM lowered blood pressure (BP) in the rat, cat, sheep, and human (12,22,26). This effect is likely mediated by a G protein receptor-coupled increase in cAMP and the local generation of nitric oxide (NO).…”

Adrenomedullin regulates intestinal physiology and pathophysiology

“…Adrenomedullin gene expression is upregulated in cardiovascular tissues of dogs with congestive heart failure due to mitral regurgitation [17], and with myxomatous mitral valvular disease [16]; in feline hearts with cardiomyopathy [13]; in lungs of pulmonary hypertensive chickens [18]; and in critically ill foals [19]. Adrenomedullin elicits a vasorelaxing effect in feline pulmonary arteries and veins [20], in bovine retinal arteries [21] and cerebral microvasculature [22], and in porcine ciliary and pulmonary arteries [23,24]. In chicks, AM seems to regulate food intake acting through hypothalamic pathways [25].…”