摘要:

The endocrine (plasma renin activity, insulin and ADH) and hemodynamic responses (heart rate and mean arterial pressure) to isoprenaline infusion were examined in conscious deoxycorticosterone-salt hypertensive rats (DS) and compared with uninephrectomized-salt control rats (US). A dose-related rise in plasma renin activity and plasma insulin values was found in US rats, while no change in either parameter was observed in DS rats after 30 min of isoprenaline infusion. ADH was not increased in US rats at any dose of isoprenaline infusion. However, in DS rats the largest dose (450 ng/kg/min) produced a significant rise. Isoprenaline infusion increased the heart rate in both groups, but the increases in the DS group were significantly lower than in the US group for the 200-ng/kg/ min dose (p < 0.01). The drop in mean arterial pressure was found to be more pronounced in DS rats than in US rats at 50, 100 and 200-ng/kg/min isoprenaline doses. Recovery of the mean arterial pressure to basal levels was also found in US rats with the various doses of isoprenaline administered. However, in DS rats the different doses of isoprenaline produced a progressive drop in mean arterial pressure with no recovery at the end of 30 min of isoprenaline infusion. The present results provide no evidence of subsensitivity to isoprenaline in the resistance vessels of conscious DS rats and suggest that the greater hypotensive response observed in these rats may be due to the inability of the renin-angiotensin system to adequately compensate the vasodilation produced by isoprenaline.

ISSN:0031-7012    

DOI:10.1159/000138522

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Both acute and chronic oral administration (1–20 mg/kg) of FCE 22716, a new ergoline derivative, resulted in a dose-related fall of arterial blood pressure lasting for more than 6 h. Tachycardia was observed only at high dosages. Yohimbine, propranolol and indometacin did not modify its antihypertensive effect; on the other hand pretreatment with prazosin, a selective α1-adrenoceptor antagonist and pithing, almost completely neutralized its antihypertensive effect. Haloperidol, a dopamine antagonist that crosses the blood-brain barrier, also antagonized FCE 22716 activity. The lack of effects of domperidone (DA2-receptor antagonist selectively acting on the periphery) together with the finding that norepinephrine and epinephrine levels were unchanged after treatment with FCE 22716, seem to rule out an involvement of peripheral DA2-receptors. Both in vitro (isolated organs) and in vivo the compound antagonized responses mediated by stimulation of α1-adrenoceptors and S2-receptors. Radioligand binding studies in different cerebral regions are in line with the above reported in vitro and in vivo results. These data suggest that FCE 22716 is endowed with a multitarget mechanism of action, mainly involving blockade of αi-adrenoceptors and S2-recep

ISSN:0031-7012    

DOI:10.1159/000138523

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

Gold-containing compounds inhibited endothelium-dependent relaxation mediated by acetylcholine and the calcium ionophore A23187 in isolated rabbit thoracic aortic rings. Auranofin was the most potent gold-containing compound studied, producing approximately 40 % inhibition of vascular relaxation at a concentration of 1 μM. Concentration-response curves to vascular relaxation produced by sodium nitroprusside were significantly shifted 5-fold to the left in the presence of auranofin. However, concentration-response curves to vascular relaxation produced by nitric oxide or isoproterenol were unaffected by auranofin. A series of other gold-containing compounds also inhibited endothelium-dependent relaxation with varying degrees of potency, but none approaching that observed with auranofin. These findings reveal that certain gold-containing compounds are potent and selective inhibitors of endothelium-dependent relaxation

ISSN:0031-7012    

DOI:10.1159/000138524

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The effects of oxyhemoglobin (oxyHb) and removal of the endothelium have been measured in isolated, perfused canine basilar arteries treated with intraluminal vasodilator drugs. In preparations with an intact endothelium, acetylcholine (ACh) produces a biphasic response, where a small vasodilation precedes a vasoconstriction. Calcium ionophore A23187 and thimerosal induce a vasodilation at low doses and a biphasic response at high doses. Sodium nitroprusside (SNP) evokes only a vasodilation. Extraluminally applied oxyHb itself produces a transient vasoconstriction and then a gradual increase in perfusion pressure. After this treatment, the vasoconstriction to ACh was enhanced as was the vasodilation to SNP. Significant attenuation of the vasodilator action of A23187 and thimerosal was also observed. Subsequent removal of endothelium produced no further change in response. This implies that the action of extraluminal oxyHb is to eliminate any endothelium-dependent responses. If cerebral vasospasm after subarachnoid hemorrhage is initiated by hemoglobin released from the clot surrounding the artery, at least one component of its action appears to involve interference with endothelial function.

ISSN:0031-7012    

DOI:10.1159/000138525

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The response of the isolated renal artery to histamine was analysed. The renal artery in relaxed state did not respond to histamine. However, in the precontracted renal artery with phenylephrine, histamine (10–8–10–4 mol/l) caused a concentration-dependent relaxation. Removal of the vascular endothelium abolished the relaxant response to smaller concentrations of histamine (108–3 × 10–63 × 10–6 mol/l). Mepyramine abolished the former response, and strongly reduced the latter response. The slight relaxant effect of histamine, resistant to mepyramine and removal of endothelium, was blocked only after combined treatment with mepyramine and metiamide. Sotalol, atropine, indometacin and diethylcarbamazine did not suppress the inhibitory effect of histamine. It is concluded that the relaxant effect of histamine on the rat renal artery is predominantly mediated by activation of H1-receptors on the endothelial cells. Only a slight component of the relaxant response to large concentrations of histamine results from activation of both H1- and H2-receptors in smooth muscle of the artery. Cyclo-oxygenase products of arachidonic acid metabolism are not involved in the mediation of the relaxant response

ISSN:0031-7012    

DOI:10.1159/000138526

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

In rats, the glutathione content of the gastrointestinal mucosa amounted to 50–60% of that of the liver. The GSH-S-transferase activity towards an aryl substrate (CDNB) was low in the stomach, colon and rectum, i.e. 5% of hepatic activity. In the small intestine there was a typical decline of activity from proximal to distal segments. GSH-Peroxidase was much lower in the intestinal mucosa as compared to the stomach and liver, whereas the GSSG-reductase was 2–3 times higher in the gastrointestinal tract in comparison to the liver. Fasting for 24 h significantly decreased the GSH content, GSH-aryltransferase and GSSG-reductase activities in the liver but not in the intestine, where even higher GSH concentrations were found in the proximal segments. L-Buthionine-sulfoximine, an inhibitor of the GSH-synthesis, caused a marked decrease of the GSH levels in the liver, stomach, proximal small intestine, colon and rectum and a concomitant decline in GSSG-reductase activity. Among the GSH-depleting agents, paracetamol exerted the strongest effect, whereas 1,1-dichloroethylene and phorone only decreased the GSH content in the liver and stom

ISSN:0031-7012    

DOI:10.1159/000138529

出版商:S. Karger AG    

年代:1989

数据来源: Karger

ISSN:0031-7012    

DOI:10.1159/000138527

出版商:S. Karger AG    

年代:1989

数据来源: Karger

摘要:

The administration of glucose to rats for 48 h resulted in an increase in the duration of anesthesia produced by intraperitoneal injection of pentobarbital. The effect of this glucose treatment on hepatic glycogen and on microsomal protein, cytochrome P450 (P450), cholesterol, lipid and phospholipid content, as well as on the spectral binding of hexobarbital and methadone to microsomal P450, was examined. The glucose treatment appeared to have no effect on microsomal protein or P450 content. The binding of hexobarbital and methadone by P450 produced a type 1 spectrum in both control and glucose-treated animals. The glucose treatment resulted in a decrease in the spectral dissociation constant (Ks) and in the maximal spectral binding (ΔAmax) of hexobarbital to P450 while with methadone there was an increase in Ks and a decrease in ΔAmax. Total lipid, phosphatidylcholine and phosphatidylethanolamine were increased in the microsomal fractions from glucose-treated animals. The changes in the parameters for drug binding to microsomal P450 probably relate to the increased lipid content of the microsomes although changes in the proportion of P450 isoenzymes could be involved. The previously observed decrease in the microsomal metabolism of hexobarbital and methadone following glucose treatment may be due to decreased binding of these compounds to microsomal P45

ISSN:0031-7012    

DOI:10.1159/000138528

出版商:S. Karger AG    

年代:1989

数据来源: Karger