A benzil and isoflavone derivatives from Derris scandens Benth.

A benzil derivative: scandione, 2',2"-dihydroxy-4'-methoxy-4",5"-methylenedioxybenzil and two isoflavones: scandenal, 3'-formyl-4',5-dihydroxy-2",2"-dimethylchromeno-[6,7:5",6"]isoflavone and scanderone, 4',5-dihydroxy-3'-prenyl-2",2"-dimethylchromeno-[7,8:6",5"]isoflavone together with fifteen known compounds were isolated from the stem of D. scandens. Their structures were determined by spectroscopic methods. Radical scavenging, antibacterial and hypertensive activities of some of the compounds were investigated.

Effects of exercise training on responsiveness of the mesenteric arterial bed to phenylephrine and KCl in male rats.

1. We aimed to determine whether there are any changes in responsiveness of the mesenteric arterial beds to phenylephrine (Phe) and KCl in exercise-trained rats, and whether vascular endothelium and/or vascular smooth muscle play a role in these changes. 2. Adult male rats were subjected to a swimming schedule every day for 28-33 days. Studies were performed in vitro using Krebs perfused mesenteric arterial beds. 3. Maximum perfusion pressure responses to KCl and Phe of the mesenteric arterial beds from exercise-trained rats were significantly lower than those from sedentary controls. However, these differences disappeared after blocking the nitric oxide synthase by NG-nitro-L-arginine (L-NOARG). 4. 3-[(3-cholamidopropyl)-dimethylammonio]-1-propanesulphonate (CHAPS, 3 mg ml(-1), 2 min infusion) caused a significant increase in maximum perfusion pressure responses to KCl to the same extent in both exercise-trained and sedentary control rats. CHAPS caused about a 4.5 fold leftward shift of the curve with no change in maximum response to Phe for the mesenteric arterial beds from sedentary control rats, but not for those obtained from exercise-trained rats. However, these differences were abolished in the presence of L-NOARG. 5. Indomethacin did not alter the dose-response curves to KCl or Phe in either swimming or control groups. 6. These results suggest that there was a lower vascular responsiveness to KCl and Phe in exercise-trained rats at rest. The decrease in reactivities to KCl or decrease in sensitivity to Phe after having endothelium impairment by CHAPS of the mesenteric arterial beds of exercise-trained rats were due to an increase in both spontaneous release and upregulation of phenylephrine-stimulated release of nitric oxide from both the vascular endothelium and the vascular smooth muscle cells, and may not be a consequence of an increase in vasodilator prostaglandins by the vascular bed.

Effect of swimming on vascular reactivity to phenylephrine and KC1 in male rats.

1. The present study aimed to examine whether there is any change in vascular responsiveness to phenylephrine and KC1 during exercise, and whether the vascular endothelium plays a role in these changes. 2. Adult male rats were subjected to a swimming schedule every day for 5-6 weeks. Studies were performed in vitro on thoracic aortae. 3. Maximum contractile response to phenylephrine of endothelium-intact thoracic aortic rings (passive tension 1.0 g) obtained from swimming rats (1.2 +/- 0.2 g, n = 8) was lower than of sedentary control rats (2.1 +/- 0.2 g, n = 8). When the endothelium was removed, however, the dose-response curves of both groups of rats were shifted to the left with an increase in maximum responses and they were no longer significantly different (max. tension, swimming rats: 3.2 +/- 0.3 g, n = 6, control rats: 3.4 +/- 0.4 g, n = 5). 4. Indomethacin did not significantly alter the dose-response curves. A similar effect to that obtained by removal of the endothelium was observed when methylene blue and indomethacin were both added. 5. Passive tension in the range of 2.5-3.0 g, caused a significant increase in active tension developed to phenylephrine (1 microM for endothelium-intact and 0.1 microM for endothelium-denuded) of thoracic aortic rings of both swimming and sedentary control rats compared to their corresponding groups when using passive tension of 1.0-1.5 g. 6. The reduction in responses to phenylephrine of endothelium-intact thoracic aortic rings of swimming rats persisted with the use of a passive tension of 3.0 g. The presence of 300 microM N0-nitro-L-arginine (LNOARG)caused a significant leftward shift of the curve with an increase in maximum responses when a passive tension of either 1.0 or 3.0 g was applied to the rings. However, for the rings with a passive tension of 1.0 g, L-NOARG caused a smaller increase in maximal contractile responses to phenylephrine of the rings of sedentary controls than those of swimming rats.7. There was no difference in the dose-response curves to depolarizing concentrations of KCl (20, 40, 80 and 120 mM) of endothelium-intact thoracic aortic rings from swimming and sedentary control rats.When the endothelium was removed, however, the dose-response curves of both groups of animals were shifted to the left with an increase in maximum responses. Moreover, the responses to KCl of endothelium-denuded thoracic aortic rings of swimming rats were greater than those of sedentary control rats.8. These results suggest that there were changes in vascular responsiveness to phenylephrine and KCl during exercise. The fall in sensitivity to phenylephrine with no change in KCl responses, and the increase in maximum responses to phenylephrine in the presence of L-NOARG in endothelium-intact aortae (passive tension 1.0 g) from swimming rats, were due to an increase in spontaneous release and upregulation of phenylephrine-stimulated release of EDRF/NO, and may not be a consequence of an increase in prostaglandins or a decrease in the production of endothelial constrictors by vascular endothelium. EDRF/NO may play an important role in modulating local vasodilatation.

Effects of pregnancy and endothelial cell removal on alpha-adrenoceptor-mediated responses of rat thoracic aortae.

1. The possibility was examined that changes in sensitivity of the aorta to alpha-adrenoceptor agonists during pregnancy in the rat are due to changes in smooth muscle receptor-mediated responses and/or endothelial cell-mediated responses. 2. Maximum constrictor responses to phenylephrine (PE) of both endothelium-intact and denuded thoracic aortic rings were greater when tissues were obtained from 20-day pregnant rats compared with non-pregnant ones. For endothelium-denuded thoracic aortic rings, the pA2 value for phentolamine as an antagonist of PE was not significantly different for rings from 20-day pregnant rats compared with rings from non-pregnant rats. 3. Prazosin (1-50 nM) markedly depressed maximum contractile responses to PE of endothelium-intact (but not denuded) thoracic aortic rings from both non-pregnant and 20-day pregnant rats. However, this marked depression of maximum responses by prazosin did not occur in the additional presence of yohimbine (10 nM), and yohimbine alone (10-500 mM) did not affect maximum responses to PE. There was no significant difference between the pA2 value for prazosin against PE-induced contractions of endothelium-denuded aortic rings obtained from either non-pregnant or 20-day pregnant rats (in the presence of yohimbine, 10 nM). 4. These results provide no evidence for a change in aortic smooth muscle alpha-adrenoceptor affinity during pregnancy, although maximum responsiveness of aortic smooth muscle to PE is increased on day 20 of pregnancy (c.f. non-pregnant controls).

Effects of endothelial cell removal on alpha-adrenoceptor-mediated responses of aortae of pregnant rats.

1. The possibility that changes in sensitivity of the aorta occurring during pregnancy in the rat are due to changes in uptake mechanisms, alpha- and/or beta-adrenoceptor-mediated responses was investigated. 2. Thoracic aortic rings from 20 day pregnant rats showed increased sensitivity to the constrictor effects of phenylephrine, with increased maximum responses when compared with those from non-pregnant animals. Removal of endothelium caused leftward shifts of the log concentration-response curves with further increases in maxima to the same extent in rings of both non-pregnant and 20 day pregnant rats. 3. Propranolol, beta-oestradiol, and nisoxetine did not significantly alter the CR-curves to phenylephrine of endothelium-intact or denuded thoracic aortic rings obtained from either non-pregnant or 20 day pregnant rats. 4. BHT-920 failed to cause marked constriction of endothelium-intact rings. After removal of endothelium, significant constrictor responses to BHT-920 occurred which were of similar magnitude for rings from both non-pregnant and 20 day pregnant rats. 5. Relaxant responses to BHT-920 of endothelium-intact rings preconstricted with phenylephrine were not significantly different between those from non-pregnant and 20 day pregnant rats. Removal of endothelium resulted in rightward shifts of the curves together with decreased maximum responses. 6. These results support earlier suggestions that the endothelium plays a role in controlling vascular reactivity to phenylephrine. The increased maximum response of thoracic aortic rings to phenylephrine seen during pregnancy does not appear to be due to marked changes in amine uptake mechanisms or beta- or alpha 2-adrenoceptor-mediated responses.

Effects of indomethacin, during pregnancy in the rat, on responses to noradrenaline and angiotensin II in vivo, and responses to phenylephrine in vitro.

Pressor responses to both angiotensin II (Ang II) and noradrenaline (NA) were reduced in 20-day-pregnant rats compared with those in non-pregnant animals, regardless of whether the results were expressed in terms of the dose per kilogram of body weight or per millilitre of estimated plasma volume. Inhibition of prostaglandin production with indomethacin (10 mg kg-1, i.v.) was not accompanied by any significant effect on responses to Ang II in either non-pregnant or 20-day-pregnant animals. However, it attenuated the effects of NA in 20-day-pregnant rats. Indomethacin (10(-5) or 3 x 10(-5) M) did not potentiate in vitro vasoconstrictor responses to phenylephrine of endothelium-intact or -denuded thoracic aortic rings from non-pregnant or 20-day-pregnant rats. These results suggest that subsensitivity to Ang II or NA during pregnancy in the rat is not due to dilution of the dose of these autacoids resulting from increased plasma volume, nor to an increased output of vasodilator prostaglandins.

Effects of endothelial cell removal on constrictor and dilator responses of aortae of pregnant rats.

1. The possibility has been examined that changes in sensitivity of the aorta occurring during pregnancy in the rat are due to changes in output of endothelium-derived relaxing factor (EDRF). 2. Concentration-isometric response curves, obtained in vitro, from thoracic aortic rings of non-pregnant rats in oestrous and 20-day pregnant rats to noradrenaline (NA) and phenylephrine (PE) were shallower with lower maxima when compared to those obtained to the thromboxane A2-mimetic U46619. 3. Removal of endothelium from aortae of non-pregnant animals caused significant shifts to the left of the curves obtained using all three agonists. In the case of NA or PE, EC50 values were reduced approximately fourfold, with maximum responses also increasing significantly. Endothelial cell removal caused an approximately eightfold increase in sensitivity to U46619 but no change in maximum response. The presence of oxyhaemoglobin (Hb) had a similar effect to endothelial removal on responses to NA and PE. 4. Rings obtained from 20-day pregnant rats showed significantly increased maximum responses to NA and PE when compared with those from non-pregnant animals. Removal of the endothelium or the presence of Hb caused significant shifts of the dose-response curves to the left and further increases in maxima. 5. In contrast, no differences in maximum responses to U46619 could be detected between the aortic rings of pregnant and non-pregnant animals. Removal of the endothelium from either caused increases in sensitivity which did not differ significantly.(ABSTRACT TRUNCATED AT 250 WORDS)

Plasma levels of atrial natriuretic peptides during pregnancy and post partum in the rat.

Plasma concentrations of atrial natriuretic peptides (ANP) in female Wistar rats were measured by radioimmunoassay at oestrus, during pregnancy, during parturition and between 3 h and 4 days post partum. Concentrations of ANP in rats on days 10, 15 and 17 of pregnancy were not significantly different from those in non-pregnant animals in oestrus (32.5 +/- 2.2 pmol/l; mean +/- S.E.M., n = 9), but levels near term (days 20 and 21 of pregnancy) were reduced by approximately 50%. However, plasma concentrations of ANP at 6, 12 and 24 h post partum were approximately twice those of non-pregnant animals in oestrus, but returned to normal levels within 4 days after parturition. Maternal plasma volume increased significantly during pregnancy, and fell 15-20% 6-24 h post partum. These results suggest that the relationship between plasma volume and the plasma concentration of ANP is reset during pregnancy and changes rapidly post partum. The results do not necessarily, however, imply any changes in the relationship between atrial pressure and the concentration of ANP.