Effect of Atrial Natriuretic Peptide and Other Vasoactive Compounds on the Uterine Vascular Bed of the Nonpregnant Sheep

Abstract

Abstract

It has been reported that atrial natriuretic peptide (ANP) concentrations are elevated in pregnancy and further elevated in pregnancy-induced hypertension. Atrial stretch and volume expansion appear to be important stimuli for ANP release. During normal pregnancy, a striking change in hemodynamics occurs that may increase plasma ANP concentrations. ANP has potent natriuretic, diuretic, and smooth muscle relaxant activities. The biological effects of ANP during pregnancy may play an important role in the physiology and pathophyisology of pregnancy. Because of possible interactions during pregnancy due to secondary effects of maternal cardiovascular changes and physiological adaptation, the present study sought to evaluate and characterize the local effects of atriopeptin II on the uterine vascular bed of the nonpregnant sheep. Ewes with catheters in the femoral artery, femoral vein, and uterine artery and electromagnetic flow probes on the middle uterine arteries were monitored for blood pressure (BP), heart rate (HR), and uterine blood flow before and after the administration into the uterine artery of bolus injections of 2, 4, 20, and 40 × 10⁻⁹ M (5, 10, 50, and 100 μg) of the synthetic ANP (atriopeptin II). For comparison purposes, the effects of prostaglandin l₂ in doses of 1.2, 2.5, 12, and 25 × 10⁻⁸ M (5, 10, 50, and 100 μg), vasoactive intestinal polypeptide in doses of 3, 9, 30, 90, 300, and 900 × 10⁻¹¹ M (0.1, 0.3, 1, 3, 10, and 30 μg), and bradykinin in doses of 9.4, 28, 94, 280, 940, and 2800 × 10⁻¹¹ M (0.1, 0.3, 1, 3, 10, and 30 μg) were also tested. Appropriate vehicles were tested and found to be without effect.

All four compounds were found to be vasodilators of the nonpregnant uterine vasculature. ANP administered into the uterine artery decreased BP (87 ± 4 mm Hg to 79 ± 4 mm Hg with 50 μg [20 × 10⁻⁹ M]), increased HR (90 ± 5 bpm to 105 ± 4 bpm), and significantly increased uterine blood flow (from 14 ± 3 to 37 ± 4 ml/min with a dose of 100 μg [40 × 10⁻⁸ M, P < 0.05]). Prostaglandin l₂ failed to alter BP, but caused significant increases on HR (100 ± 4 to 124 ± 13 bpm, P < 0.05) and uterine blood flow (17 ± 4 to 73 ± 10 ml/min, P < 0.05). Vasoactive intestinal polypeptide caused a significant tachycardia (97 ± 10 to 158 ± 9 bpm, P < 0.05) at the highest dose, Bradykinin increased BP significantly at two of the highest doses. These data indicate that local intra-arterial bolus injections of ANP not only caused local uterine effects, but also had significant effects on BP and HR, which were qualitatively similar to those produced by vasoactive intestinal polypeptide. [P.S.E.B.M. 1992, Vol 201]