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The aim of this study was to determine if placental prostanoids could mediate the vasodilating action of an alpha-1-adrenoceptor antagonist, nicergoline (400 micrograms/kg i.p.), during late pregnancy in streptozotocin-induced diabetic rats (40 mg/kg i.v.). Placental prostanoid concentrations were evaluated by radioimmunoassay. Prostaglandin E2 levels showed a highly significant increase in diabetic and nondiabetic rats treated with nicergoline (p less than 0.001). 6-Keto-PGF1 alpha concentrations were slightly increased in diabetic rats compared to controls, and this increase was reversed by both nicergoline and insulin treatments. In all groups studied thromboxane B2 levels were comparable. It is concluded that prostaglandin E2 could mediate the vasodilating action of nicergoline on the placental irrigation and, therefore, improved the hemodynamic state of this organ in diabetic rats.

Female rats rendered diabetics following administration of streptozotocin (40 mg/kg/day I.V.) on the fifth day of pregnancy received daily injections of nicergolin) 200 micrograms/kg/day or 400 micrograms/kg/day I.P.) from day 5 through day 19 of gestation, when animals were sacrificed. It was found that nicergoline significantly reduces the frequency of abortions increases the weight of foetuses and placentas when compared to control diabetic rats. These effects are due neither to a maternal or foetal reduction of glycemia nor to modifications of insulinemia or the levels of sexual hormones of the mother. Histopathological examination of the placentas confirms the positive effect of nicergolin and appears to be due to a direct vascular action.

The effects of two adrenoceptor antagonists, nicergoline (alpha 1) and acebutolol (beta 1), on the contraction of myometrium in the proestrous rat were compared to those of noradrenaline and phentolamine. The spontaneous myometrial contractions of Wistar rats on the day of proestrus were recorded isometrically and the data were analysed using Wilcoxon non-parametric statistics. All drugs were administered i.v. and the doses are expressed as microgram/kg body weight. Noradrenaline (1200 micrograms/kg per h) induced a 32.5% reduction (P less than 0.001) of the uterine contraction amplitude. Nicergoline did not alter uterine motility significantly when administered alone at doses ranging from 400 to 1600 micrograms/kg. However, successive injections of nicergoline in the same range given during noradrenaline infusion at 600 micrograms/kg per h potentiated the relaxing action of the latter (38%, P less than 0.01). Phentolamine (120 micrograms/kg) reduced myometrial activity by 25% (P less than 0.05). This inhibitory response rose to 65% (P less than 0.001) when the dose of phentolamine was increased to 960 micrograms/kg. When a single injection of nicergoline (400 micrograms/kg) was followed by the administration of increasing doses of acebutolol (120, 1200, 2400 micrograms/kg) the slight inhibitory effect on uterine motility observed after administration of each of the two agents separately became more pronounced (P less than 0.05). It appears from these results that combining noradrenaline with nicergoline and nicergoline with acebutolol leads to potentiation of their relaxing effects. Furthermore the results confirm that nicergoline is a partial alpha-blocker.

A randomised crossover study in eleven diabetic patients with arteritis compared the effects of nicergoline (2,5 mg i.v.) or placebo on haemodynamic and metabolic parameters after exercise tests. Haemodynamic modifications after effort following placebo administration were typical: raised systolic blood pressure, and increased heart rate and myocardial oxygen requirements (systolic BP x heart rate). Modifications after similar effort following nicergoline involved an increase in systolic B.P. only, heart rate and myocardial oxygen requirements remaining unchanged. Blood lactic acid levels after effort and treatment were significantly higher (p. less than 0.01) than after effort without treatment. Overall metabolic and haemodynamic results demonstrate an increase in effort tolerance in diabetic patients with arteritis after nicergoline, this having been previously observed in healthy subjects.