Effects of the combined ETA and ETB receptor antagonist PD145065 on arteries, arterioles, and veins in the cat hindlimb

Ekelund, UlfLund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine (author)

The aim of this study was to describe in quantitative terms the effects of ETA and ETB receptor blockade on vascular tone (resistance) in large-bore arterial resistance vessels (> 25 microns), small arterioles (< 25 microns), and veins in the cat gastrocnemius muscle in vivo. In the muscle vascular bed, the combined ETA and ETB receptor antagonist PD145065 (1 mg/kg/min, intra-arterially) abolished the biphasic vascular responses (dilatation followed by constriction) to both ET-1 (0.4 microgram/kg/min, intra-arterially) and to the selective ETB receptor agonist IRL1620 (3.2 micrograms/kg/min, intra-arterially). In the cat femoral artery and vein in vitro, PD145065 competitively inhibited the contractile responses to both ET-1 and IRL1620. The contractile response to the latter agonist could be evoked only after long-term incubation of the vessels (37 degrees C for 5 days). These results indicate that PD145065 is a potent antagonist at both ETA and ETB receptors in vivo and in vitro. Therefore, this antagonist may prove useful for elucidating the possible physiologic and/or pathophysiologic roles of the endothelins. For example, it was shown that PD145065 had no effect on vascular tone in the resting state, indicating no role for the endothelins in the regulation of basal vascular tone in cat skeletal muscle.

Adner, MikaelLund University,Lunds universitet,Klinisk och experimentell allergiforskning,Laryngoesofagologi, allergi och livskvalitet,Forskargrupper vid Lunds universitet,Clinical and Experimental Allergy Research,Laryngoesophagology, Allergy and Life Quality,Lund University Research Groups(Swepub:lu)oron-mad (author)
Edvinsson, LarsLund University,Lunds universitet,Medicin, Lund,Sektion II,Institutionen för kliniska vetenskaper, Lund,Medicinska fakulteten,Medicine, Lund,Section II,Department of Clinical Sciences, Lund,Faculty of Medicine(Swepub:lu)med-led (author)
Mellander, StefanLund University,Lunds universitet,Institutionen för experimentell medicinsk vetenskap,Medicinska fakulteten,Department of Experimental Medical Science,Faculty of Medicine(Swepub:lu)mphy-sme (author)
Medicin, LundSektion II (creator_code:org_t)

By the author/editor: Ekelund, Ulf; Adner, Mikael; Edvinsson, Lars; Mellander, Stefa ...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Respiratory Medi ...

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MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Clinical Medicin ...; and Other Clinical M ...

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