The effect of pregnancy on the response to the TxA2/PGH2 analogue U-46619 in rabbits

Abstract

We compared the hemodynamic actions of U-46619, a stable thromboxane A2 (TxA2) prostaglandin H2 (PGH2) analogue, in nonpregnant (NP) rabbits with those observed in late pregnant (P) rabbits. An intravenous injection of U-46619 (10 micrograms) to each of eight NP chronically instrumented rabbits (mean body weight 3.4 kg) induced an immediate (1 min) and reversible fall of cardiac output (CO, 66%) and mean arterial pressure (MAP, 41%, both P < 0.01). P rabbits (n = 6, mean body weight 3.8 kg), however, responded with an elevation of MAP (5%, P < 0.02) upon intravenous injection of the drug (10 micrograms), while CO remained unchanged. The fall of CO in NP rabbits was associated with the temporary disappearance of a fraction of circulating platelets between the superior vena cava and the aortic arch. The number of platelets at 30 and 60 s after U-46619 was reduced (P < 0.05) by 14 and 20% respectively in the aortic blood, whereas caval platelet counts were unchanged until 90 s (-6%, P < 0.05). In contrast, intraaortic administration of this drug (10 micrograms) to NP rabbits resulted in neither thrombocytopenia nor hypotension. U-46619 (10-30 micrograms i.v.) caused no decrease in platelet count in the aorta of P rabbits. In vitro, U-46619-induced aggregation of platelets harvested from P rabbits was also blunted (P < 0.001). This could not be attributed to reduced affinity or number of platelet thromboxane receptors. The data indicate that U-46619 induces a fall of arterial pressure simultaneous with intravascular platelet aggregation.(ABSTRACT TRUNCATED AT 250 WORDS)

The vasoconstrictor effects of L‐NAME, a nitric oxide synthase inhibitor, in pregnant rabbits

“…kg measured in both P and NP rabbits of the present study. Further, TPRI was proportionately higher by about 70%, in both P and NP rabbits, under anaesthesia than in conscious P and NP rabbits (Losonczy et al, 1993;1995). Thus, anaesthesia and surgery do not seem to influence differentially baseline haemodynamics in NP and P rabbits and the pregnancy-induced falls in MAP and TPR were well maintained.…”

“…However, in conscious, chronicallyinstrumented rabbits COI was around 200 ml min-'. kg in both P and NP animals (Losonczy et al, 1993;1995) Gy. Losonczy et at Nhric oxide and blood pressure in rabbit pregnancy compared to the value of 150 ml min .…”

Animal models of preeclampsia

“…These effects were independent of angiotensin II whereas cyclooxygenase inhibition and thromboxane A2/prostaglandin H2 receptor blockade prevented the pressor response to reductions in uteroplacental perfusion pressure. 16 Later studies in pregnant rabbits [17][18][19] and rats, 20 showed that agonists of the thromboxane A2/prostaglandin H2 receptors are more potent hypertensive substances than in nonpregnant controls, a finding that, together with that of Woods, 16 supports a role for thromboxane A2 as a potential mediator of preeclamptic hypertension. Abitol et al also observed marked increases of BP in conscious dogs in response to chronic uteroplacental ischemia, 21 although BP was very variable in controls.…”

Enhanced vascular effects of the Ca2+channel agonist Bay K 8644 in pregnant rabbits

“…CONSCIOUS, CHRONICALLY INSTRUMENTED RABBITS: The protocol followed was described previously in similar studies (10,19,20). After induction of general anesthesia, the left femoral artery was isolated and catheterized so that the catheter tip lay in the distal aorta.…”

“…All experiments were undertaken in a quiet room. MAP and HR were measured using the Cardiomax II System (Columbus Instruments) via the arterial line (10,19,20).…”