摘要:

42 female rats (230–260 g) made hypertensive by bilateral renal encapsulation with latex envelopes were divided into three equal groups. Two groups were administered the angiotensin-converting enzyme inhibitor captopril (SQ 14,225) in drinking water at a concentration sufficient to yield a dose of 25 and 50 mg/kg/day, respectively. The third group was untreated. A fourth group (14 rats) served as a normotensive control group. Systolic blood pressures and body weights were measured weekly during a 4-week control and an 8-week experimental period. Both doses prevented the elevation of blood pressure to the level of the untreated hypertensive controls. Blood pressure of the group receiving the higher dose of captopril was within the range of that of the normotensive control group by the end of the experiment while that of the group receiving the lower dose was between the blood pressures of untreated hypertensive and normotensive controls. Renal encapsulation resulted in failure of the rats to grow normally. Administration of captopril at either dose had no additional effect on body weight. To test whether inhibition of the angiotensin-converting enzyme occurred at the doses of captopril used, angiotensin I (200 µg/kg s.c.) and bradykinin (200 µg/kg s.c.) were administered separately and their effects on water intakes of control and captopril-treated groups tested. Captopril inhibited the drinking response to angiotensin I while increasing it in response to bradykinin. The pressor response following intravenous administration of 1.25 µg angiotensin I/kg to anesthetized rats was also studied. The groups treated with captopril had a significantly reduced response to angiotensin I compared with those of either normotensive or hypertensive groups. The results of the three tests suggest that inhibition of the angiotensin-converting enzyme occurred at both doses of captopril, with the higher dose inducing a somewhat greater inhibition. At autopsy, heart weight of the group receiving the higher dose of captopril was significantly less than that of the untreated hypertensive group, but significantly greater than that of the normotensive group. These results also suggest that captopril, at the doses used, provided significant protection against elevation of blood pressure in renal hypertensive

ISSN:0031-7012    

DOI:10.1159/000137502

出版商:S. Karger AG    

年代:1981

数据来源: Karger

摘要:

The effects of two Ca antagonists, diltiazem (DZ) and verapamil (VP), on norepinephrine (NE)-stimulated 45Ca uptake in vascular smooth muscle from New Zealand White rabbit aortas were studied. Data were collected before, at 10, 30, and 60 min after drug addition, and during a simultaneous control period without drug addition. NE alone (6 × 10–6M) significantly increased 45Ca uptake from the extracellular space presumably by activating the receptor-operated Ca channel during excitation-contraction coupling. This effect was maximal by 10 min after NE addition and stable through the 60-min time point. Both VP (5 × 10–5M) and DZ (2.2 × 10–7M) inhibited the NE-stimulated 45Ca uptake at the 10- and 60-min time points, respectively. These data demonstrate that both DZ and VP inhibit 45Ca uptake from the extracellular space during activation of the receptor-operated Ca channel with NE. The effects of DZ and VP to inhibit NE-stimulated 45Ca uptake are demonstrated at concentrations which have been previously shown to cause dilation of vascular smoot

ISSN:0031-7012    

DOI:10.1159/000137503

出版商:S. Karger AG    

年代:1981

数据来源: Karger

摘要:

In order to evaluate whether peripheral and/or cardiac α-adrenoceptors were involved in the cardiac effects of sympathomimetic drugs, the effects of phenoxybenzamine (1 mg/kg body weight) on increasing, graded doses of dobutamine, etilefrine and xylometazoline were investigated in anesthetized dogs. Measurements were made of simultaneous changes in left ventricular pressure, rate of rise of left ventricular pressure (dP/dt), aortic blood pressure, peripheral blood flow as well as heart rate. To determine the actual contractile responses independent of hemodynamic influences on the myocardium, all drugs were studied under conditions of fixed mean aortic pressure and heart rate. Dobutamine produced increases in dP/dtmax which remained unaffected by phenoxybenzamine, whereas the blood pressure increase was antagonized. The contractile responses, however, were less pronounced under fixed blood pressure conditions demonstrating that part of the inotropic response to dobutamine is attributable to an α-receptor-mediated increase of the afterload. The primary effect on myocardium is assumed to be mediated by β1-receptors. In contrast to conditions of uncontrolled hemodynamics, etilefrine produced only small increases in contractility. Since these effects were antagonized by phenoxybenzamine and phentolamine (0.5 mg/kg body weight), it can be postulated that the canine heart contains a population of adrenergic α-receptors. However, a further subtype of α-receptor must exist, since xylometazoline produced negative inotropic responses which were prevented by phenoxybenzamine and were even potentiated when α-receptor-mediated increase of the afterload was eliminated by fixing the blood pressure. Apart from α-receptors situated in the myocardium, the sinus node must also contain both receptor subtypes since the positive chronotropic response to etilefrine as well as the negative chronotropic response to xylometazoline were inhibited by phenoxyben

ISSN:0031-7012    

DOI:10.1159/000137504

出版商:S. Karger AG    

年代:1981

数据来源: Karger

摘要:

Promethazine and cimetidine blocked the hypotensive actions of 2-pyridylethylamine, an H1 agonist and dimaprit, an H2 agonist, respectively, but not that of bovine parathyroid hormone fragment [bPTH-(1-34)]. Rats were treated repeatedly with the histamine releaser, compound 48/80, until the releaser could no longer produce a decrease in blood pressure. The hypotensive action of bPTH-(1-34) could still be seen. Rats with histamine partially depleted with one injection of compound 48/80 were injected with cimetidine and pyrilamine, an H1antagonist, which together blocked the hypotensive action of subsequent injections of compound 48/80, but not that of bPTH-(1-34). These data suggest that the vasodilatory action of bPTH-(1-34) does not involve the release or action of histamine.

ISSN:0031-7012    

DOI:10.1159/000137505

出版商:S. Karger AG    

年代:1981

数据来源: Karger

摘要:

LR 19731 [4-β-chlorophenyl-5-β-(N’-phenyl)piperazinoethyl-l,3-dioxolin-2-one] lowers the plasma cholesterol and triglyceride levels of rats in several experimental conditions after single or repeated treatments, while it is scarcely active on liver lipids. The compound is especially effective in reducing plasma cholesterol in a dose-related manner both in normolipemic and hyperlipemic rats. The minimal effective dose (after five oral treatments in 4 days to normolipemic rats) is as low as 3 mg/kg, the ED50 is 11.3 mg/kg, while the maximal effective dose capable of completely suppressing plasma cholesterol is 100 mg/kg. Surgical removal of the thyroid gland does not influence its activity. At its ED50 the compound does not cause hepatomegaly, accumulation of desmosterol in plasma and liver. Under the same experimental conditions clofibrate presents a poor dose-response correlation on plasma lipids and generally appears at least 10 times less active than LR 19731 on cholesterol but more effective on liver weight. The experiments of general pharmacology indicate that LR 19731 does not affect central and peripheral nervous functions, does not influence the cardiovascular system or cause skeletal muscle relaxation, hypothermia, analgesia, and does not possess anti-inflammatory properties up to a dose of about 100 mg

ISSN:0031-7012    

DOI:10.1159/000137506

出版商:S. Karger AG    

年代:1981

数据来源: Karger

摘要:

Quantitative estimations of glutathione S-transferase activities with 1-chloro-2,4-dinitrobenzene as the electrophilic second substrate, in 142 postmortem human tissue specimens derived from 34 different organs of one or more of 13 individuals belonging to various age groups, are presented. Collectively the data indicate: (1) all tissues examined have appreciable levels of enzyme activity; (2) liver, kidney, lung, muscle, heart, adrenal glands, pancreas, and stomach of fetal origin possess higher enzyme activities than those of the adults, and (3) there are wide interindividual variations in the tissue enzyme activities.

ISSN:0031-7012    

DOI:10.1159/000137507

出版商:S. Karger AG    

年代:1981

数据来源: Karger

摘要:

The distribution of primaquine was measured in seven rat tissues at 15–180 min after the intraperitoneal injection of the antimalarial 8-aminoquinoline. The half-life of unmetabolized primaquine was 4.0 h in lung, 1.7–1.9 h in blood, spleen, kidney and heart, and 1.2 h in liver. At each interval, the concentrations of unmetabolized primaquine were (in order): lung > liver, kidney, spleen > heart > brain ≧ blood. At 3 h after the injection of [6-O-methyl-3H]primaquine, unmetabolized primaquine constituted 10% of the total 3H in blood and 40–60% of the total 3H in liver, brain, heart and

ISSN:0031-7012    

DOI:10.1159/000137508

出版商:S. Karger AG    

年代:1981

数据来源: Karger