ALPHA1-ADRENERGIC RECEPTORS IN PULMONARY AND SYSTEMIC VASCULAR SMOOTH-MUSCLE - ALTERATIONS WITH DEVELOPMENT AND PREGNANCY

α1-Adrenergic receptors mediate vasoconstriction in the pulmonary and systemic vasculature. In sheep the in vivo vasoconstrictor response to α1-adrenergic stimulation is less in the pulmonary circulation compared with the systemic circulation of the fetus, the response increases in both vascular beds with fetal and postnatal development, and it decreases in the systemic vasculature with pregnancy. In an effort to determine the mechanisms underlying these differences, α1-adrenergic receptor binding characteristics were determined by using [3H]prazosin in intrapulmonary and systemic (thoracic aorta) vascular smooth muscle (VSM) from late-gestation fetal lambs and from pregnant and nonpregnant ewes. α1-Adrenergic receptor density was less in fetal intrapulmonary VSM that in fetal aortic VSM (12.4 ± 1.5 versus 29.4 ± 3.2 fmol/mg protein, p < 0.05), and it was less (p < 0.05) in the fetus compared with the pregnant ewe in both intrapulmonary and aortic VSM (51.0 ± 5.2 and 76.5 ± 5.9 fmol/mg protein, respectively). α1-Adrenergic receptor density in intrapulmonary VSM was similar in the pregnant and nonpregnant ewe (61.9 ± 7.2 fmol/mg protein), whereas in aortic VSM it was less (p < 0.05) in pregnant ewes compared with nonpregnant ewes (101.0 ± 5.5 fmol/mg protein). α1-Adrenergic receptor affinity was similar in all the VSM sources tested. β-Adrenergic receptor density was studied for comparison, and it was similar in intrapulmonary and aortic VSM and unchanged in the fetus versus the pregnant ewe (18.9 ± 3.0 versus 19.3 ± 2.7 versus 23.0 ± 5.8 versus 14.5 ± 2.9 fmol/mg protein in fetal intrapulmonary, fetal aortic, adult intrapulmonary, and adult aortic VSM, respectively). Thus, there are differences between vascular beds, maturational changes, and pregnancy-associated alterations in VSM α1-adrenergic receptor density that are specific to this adrenergic receptor type. It is speculated that these differences in receptor number may partly explain the disparate vasoconstrictor responses to α1-adrenergic stimulation found in the pulmonary vasculature compared with the systemic vasculature, in the fetus compared with the adult, and in the pregnant state compared with the nonpregnant state.