Acute hypoxic vasoconstriction in isolated rat small and large pulmonary arteries.
Hypoxic vasoconstriction (HPV) has been shown to consist of a biphasic contraction change. The first phase of the hypoxic response peaks at approximately five minutes. The second phase is at about 30 minutes. The force of contraction of both phases of HPV were found to be significantly greater in pulmonary resistance vessels (PRV) than in pulmonary artery (PA) (P < 0.01). The endothelium modulates the hypoxic response, especially of the second phase of HPV (68% reduction in PRV) (P < 0.05). In Ca(2+)-free solution, the first peak and the second peak of HPV were reduced to 11 and 32% contraction in PRV and to 26 and 21% contraction in PA. A calcium channel antagonist (amlodipine) caused significant dose-dependent inhibition of the first phase of HPV (P = 0.001), with a significantly greater effect on PRV compared to PA (P < 0.01). Levcromakalim caused a dose-dependent inhibition of HPV in PRV (58% at 10 microM). In contrast, HPV in PA was not significantly inhibited by levcromakalim. In conclusion, this study has confirmed that hypoxia induces a biphasic contractile response in isolated pulmonary arteries requiring extracellular calcium. Both amlodipine and levcromakalim inhibit hypoxic pulmonary vasoconstriction and these agents may be of value in the treatment of pulmonary hypertension.
Zhang
F
F
Department of Medicine and Pharmacology, University of Sheffield, UK.
Woodmansey
P A
PA
Morice
A H
AH
D000208:Acute Disease; D017311:Amlodipine / Q000494:pharmacology; D000818:Animals; D001578:Benzopyrans / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D019806:Cromakalim; D004730:Endothelium, Vascular / Q000378:metabolism; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology*; D066298:In Vitro Techniques; D008297:Male; D011651:Pulmonary Artery / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology*; D011758:Pyrroles / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D001578:Benzopyrans; D002121:Calcium Channel Blockers; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D017311:Amlodipine