Gender differences in pulmonary arterial reactivity to dilatory agonists in pulmonary hypertension.
OBJECTIVE
To determine whether impaired reactivity to dilatory agonists could contribute to pulmonary hypertension, and whether there are gender differences in pulmonary vasodilator reactivity.


METHODS
Pulmonary arterial rings from monocrotaline (MCT)-induced pulmonary hypertensive and control rats were isolated. At the peaks of submaximal contractions to norepinephrine (NE) or endothelin (ET-1), rings were exposed to 5 x 10(-6) M acetylcholine (ACh) or 9 x 10(-9) M adrenomedullin (ADM) or 1.3 x 10(-8) M calcitonin gene-related peptide (CGRP).


RESULTS
Relaxation to ACh, ADM, and CGRP was endothelium-dependent. Hypertensive pulmonary arterial rings relaxed less to ACh and CGRP than controls in both genders. Female pulmonary hypertensive muscle was more rather than less reactive to ADM compared with controls. ADM-induced relaxation of NE contractions was 2.4 times greater in female compared with male control rings and 5.5 times greater in female compared with male hypertensive preparations. Gender differences in relaxation responses were similar for CGRP. MCT-treated female arterial rings relaxed more than did MCT-treated male arterial muscle in response to ACh. No difference in ACh relaxation was found between genders for controls.


CONCLUSIONS
Pulmonary arterial relaxation to endothelium-dependent vasodilators is impaired in MCT-induced pulmonary hypertension with the exception of ADM in females. Vasodilators may be more effective in reducing pulmonary hypertension in females than in males.
D000109:Acetylcholine / Q000494:pharmacology; D053607:Adrenomedullin; D000818:Animals; D015740:Calcitonin Gene-Related Peptide / Q000494:pharmacology; D016232:Endothelins; D005260:Female; D006976:Hypertension, Pulmonary / Q000139:chemically induced*; D008297:Male; D016686:Monocrotaline; D009638:Norepinephrine; D010455:Peptides / Q000494:pharmacology; D011651:Pulmonary Artery / Q000187:drug effects*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012723:Sex; D014664:Vasodilation / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
D016232:Endothelins; D010455:Peptides; D014665:Vasodilator Agents; D053607:Adrenomedullin; D016686:Monocrotaline; D015740:Calcitonin Gene-Related Peptide; D000109:Acetylcholine; D009638:Norepinephrine