Gender differences in pulmonary arterial reactivity to dilatory agonists in pulmonary hypertension.

Objectives: 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.