FETAL PULMONARY VASODILATION WITH HISTAMINE: MEDIATION BY H1 AND H2 RECEPTORS

Abstract

Histamine (H) is known to dilate the fetal pulmonary circulation. The receptor characteristics, however, have not been completely described. To do so, we determined dose response curves (DRC) to H and to H with infusion of H1 and/or H2 antagonists in 6 chronically prepared fetal sheep. A cuff electromagnetic flow probe measured blood flow to the left lung (QL). Catheters in the main pulmonary artery and aorta measured pressure. A left pulmonary artery (LPA) catheter allowed local infusion of H thereby minimizing systemic effects. QL increased logarithmically from H doses of 1/2 ng·kg⁻¹ to 16 ng·kg⁻¹. At H = 16 ng·kg⁻¹, QL was 110% over baseline. The DRC plateaued at larger H doses. All H doses up to 125 ng·kg⁻¹ had no effect on systemic or pulmonary pressure or on heart rate. Diphenhydramine (D), an H1 antagonist, given systemically, shifted the DRC to the right with a dose ratio of 26. Cimetidine (C), an H2 antagonist, had a similar effect with a dose ratio of 1.5. Simultaneous D and C resulted in a dose ratio of 55. H1 and H2 receptors were further confirmed by the use of specific H1 (2-pyridylethylamine) and H2 (Dimeprit) agonists. We conclude that the marked sensitivity of the fetal pulmonary circulation to H is mediated through both H1 and H2 receptors. These findings contrast with those of previous studies in the hypoxic adult pulmonary circulation where atypical H2 receptors may be present, but agree with findings in the hypoxic newborn lamb.

Log in or create a free account to read this content

Gain free access to this article, as well as selected content from this journal and more on nature.com

Access through your institution

or

Sign in or create an account

Continue with Google

Continue with ORCiD