NITRIC-OXIDE AND VASCULAR REACTIVITY IN PREGNANT RATS WITH ADRIAMYCINNEPHROPATHY

1. In previous studies we have shown that, after the administration of adriamycin, hypertension developed in rats who became pregnant (adria mycin-pregnant rats), whereas virgin animals remained normotensive. Su bsequently, we showed that this hypertension was prevented by administ ration of L-arginine, suggesting that deficient synthesis of nitric ox ide may be pathogenetic in this model. 2. To further assess the role o f nitric oxide in this model, we measured mean arterial blood pressure after administration of L-arginine to adriamycin-pregnant rats or of N-G-nitro-L-arginine-methyl ester (L-NAME) to normal pregnant rats. In other experiments, we assessed the response of isolated perfused arte rial mesenteric vessels, precontracted with noradrenaline, to acetylch oline, L-arginine or L-NAME. 3. Blood pressure was decreased in normal pregnant rats, whereas it was elevated in adriamycin-pregnant rats. L -NAME treatment increased blood pressure in normal pregnant rats and L -arginine decreased it in adriamycin-pregnant rats. 4. Mesenteric vess els of adriamycin-pregnant rats exibited an exaggerated vasoconstricto ry response to noradrenaline, when compared with the blunted response observed in normal pregnancy. The addition of L-NAME in vitro induced a further contraction, significantly greater in normal pregnant rats. The vasodilatory response to acetylcholine and L-arginine was greater in vessels from adriamycin-pregnant rats. In contrast, responses to ei ther nitroprusside or diazoxide were similar in all groups. 5. The res ults suggest a state of reduced nitric oxide synthesis in rats with ad riamycin nephropathy, leading to vascular maladaption and hypertension in pregnancy.