ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The mechanism by which monoclonal antibodies directed against human renin (R3-36-16 and R3-47-10) inhibit renin activity was investigated using various substrates. Both antibodies acted as potent inhibitors of human renin activity when human angiotensinogen was used as a substrate. However, their effects differed clearly in the presence of synthetic tetradecapeptide. When low concentrations of tetradecapeptide were used as substrate, renin activity was only partially inhibited by R3-47-10, whereas it was stimulated by R3-36-16. At higher synthetic substrate concentrations, both antibodies stimulated angiotensin I production. This effect was independent of the pH. Both antibodies exerted their effects in the presence of CGP 29287, a peptidic transition-state competitive renin inhibitor, indicating that their binding sites differed from that of CGP 29287. In combination, the stimulatory effect of R3-36-16 was not blocked by R3-47-10, but the inhibition produced by R3-47-10 was reversed by R3-36-16. Both antibodies may prevent the large natural substrate angiotensinogen from entering the enzymatic cleft by steric hindrance. At a low substrate concentration, R3-47-10 may also partially hinder the access of synthetic tetradecapeptide into the active cleft by steric hindrance. In contrast, the stimulating effect of both antibodies may be due to a conformational change in the renin molecule, allowing an increased access of tetradecapeptide or a more rapid release of the product from the enzymatic cleft.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The sequence and magnitude of acute changes in renal blood flow following administration of captopril were determined in a canine model of acute unilateral renal artery stenosis using rubidium-82 and positron emission tomography. Data were recorded in each of nine dogs under three conditions: 1) during a baseline control interval, 2) during renal artery stenosis, and 3) during stenosis with intravenous injection of captopril (1.2 mg/kg). Mean arterial blood pressure was 108 ± 12 mm Hg at control, increased significantly to 125 ± 13 mm Hg (p< 0.01) during stenosis, and decreased to 98 ± 13 mm/Hg (p< 0.01) after captopril infusion. Mean renal blood flow was calculated using a steady state single compartment model from the images produced by positron emission tomography. The estimated flow to the affected kidney was 3.37 ± 1.48 ml/min/g at control, 0.86 ± 0.62 ml/min/g during stenosis (p< 0.01), and 0.64 ± 0.57 ml/min/g after captopril administration (p= NS compared with precaptopril value). The estimated flow to the contralateral kidney was minimally reduced from a baseline of 3.84 ± 0.95 to 3.24 ± 1,13 ml/min/g (p=NS) during stenosis and increased after captopril infusion (4.08 ± 0.94 ml/min/g; p=0.01). These data suggest that repetitive imaging with positron emission tomography can be used to delineate acute changes in renal perfusion following captopril administration. (Hypertension 11: 217–222, 1988).

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Isolated rat hindlegs were perfused with Krebs-Ringer solution, and immunoreactive angiotensin II (irAng II) released into the perfusate was directly determined using a Sep-Pak C18cartridge connected to the perfusion system. High performance liquid chromatography clearly demonstrated the presence of angiotensin I (Ang I), angiotensin II (Ang II), and a small amount of angiotensin III. The spontaneous release of irAng II was as high as about 600 pgβ0 min, which was stable up to 3 hours. Captopril added to the perfusion medium (10−9to 10−6M) suppressed irAng II release in a dose-dependent manner (p< 0.001), and it (10−6M) caused a reciprocal increase of irAng I release (p< 0.05). Oral pretreatment of captopril (50 mg/kg/day) for 1 week suppressed the irAng II release by 31 % (p< 0.02). The same treatment with SA446, a highly lipophilic angiotensin converting enzyme inhibitor, inhibited the irAng II release by 63% (p< 0.001). On the other hand, the two inhibitors suppressed the plasma irAng II to very similar extents. Pretreatment with SA446 plus nephrectomy did not cause any further change in irAng II release as compared with that with SA446 alone. These results provide direct proof for local generation and subsequent secretion of Ang II by peripheral vascular tissue.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Inhibition of angiotensin converting enzyme (ACE) in serum and tissues of rats was studied after administration of lisinopril, an ACE inhibitor. Tissue ACE was assessed by quantitative in vitro autoradiography using the ACE inhibitor [125I]351A, as a ligand, and serum ACE was measured by a fluorimetric method. Following oral administration of lisinopril (10 mg/kg), serum ACE activity was acutely reduced but recovered gradually over 24 hours. Four hours after lisinopril administration, ACE activity was markedly inhibited in kidney (11% of control level), adrenal (8%), duodenum (8%), and lung (33%;p< 0.05). In contrast, ACE in testis was little altered by lisinopril (96%). In brain, ACE activity was markedly reduced 4 hours after lisinopril administration in the circumventricular organs, including the subfornical organ (16–22%) and organum vasculosum of the lamina terminalis (7%; p < 0.05). In other areas of the brain, including the choroid plexus and caudate putamen, ACE activity was unchanged. Twenty-four hours after administration, ACE activity in peripheral tissues and the circumventricular organs of the brain had only partially recovered toward control levels, as it was still below 50% of control activity levels. These results establish that lisinopril has differential effects on inhibiting ACE in different tissues and suggest that the prolonged tissue ACE inhibition after a single oral dose of lisinopril may reflect targets involved in the hypotensive action of ACE inhibitors.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Plasma glucose and insulin responses to both a 75-g oral glucose challenge and to conventional meals were determined in eight patients with hypertension and compared with values of a control population. The results indicated that patients with hypertension had significantly higher than normal plasma glucose and insulin concentrations in both situations. Furthermore, when dietary carbohydrate was increased by 16% of total calories (with a reciprocal reduction in dietary fat), the hyperglycemia and hyperinsulinemia present in patients with hypertension were accentuated. Since low fat-high carbohydrate diets are usually recommended for patients with hypertension, these data suggest that abnormalities of glucose and insulin metabolism associated with hypertension would be increased if patients with high blood pressure followed conventional dietary advice. Since hyperglycemia and hyperinsulinemia have been shown to be associated with an increased risk of developing coronary artery disease, it may be appropriate to reevaluate the clinical utility of low fat-high carbohydrate diets in the treatment of hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Potential predictors of systolic and diastolic blood pressure change between 1960 and 1967 in the biracial population of Evans County, Georgia, were investigated. An all possible regressions multiple linear regression analysis was used. For systolic blood pressure change, the level of systolic blood pressure, age, and change in Quetelet index were significant (p < 0.05) correlates in white men. The level of systolic blood pressure, the level and change of socioeconomic status, change in Quetelet index, and change in cholesterol were significant correlates for white women. The level of Quetelet index was of borderline significance (p < 0.055) when the other significant variables were included in the model for white women. The change in Quetelet index was the only significant correlate of systolic blood pressure change in blacks. For diastolic blood pressure change, age, change in hematocrit, and change in Quetelet index were significant correlates for white men. Age, level and change of socioeconomic status,'level and change of Quetelet index, and change in hematocrit were the significant correlates in white women. In black men, change in Quetelet index and age were significant. In black women, only age was a significant correlate of diastolic blood pressure change. These results indicate that there may be important differences in these correlates between race-sex groups and thus in the mechanism of blood pressure change for different race-sex groups.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The local hemodynamic effects of serotonin (5-hydroxytryptamine; 5-HT) and the selective 5-HT2antagonist ketanserin were investigated in the forearm of 20 healthy volunteers. Single doses of 5-HT (0.1–80 ng/kg/min) and ketanserin (5–125 ng/kg/min) were administered intra-arterially. The relative α1-adrenergic receptor and 5-HT2blocking potencies of ketanserin were investigated using intra-arterial infusions of cumulative doses of methoxamine (0.1, 0.3, and 0.5 μg/kg/min), tyramine (0.25, 0.50, and 1.25 μg/kg/min), and 5-HT (10, 30, and 80 ng/kg/min) together with a low dose (5 ng/kg/min) and a high dose (50 ng/kg/min) of ketanserin. Forearm blood flow was measured by venous occlusion plethysmography. Heart rate and intra-arterial blood pressure were recorded semicontinuously. Intra-arterial infusion of 5-HT induced an initial transient vasodilatation, followed by a steady vasodilatation for the low doses of 5-HT (0.1–10 ng/kg/min; p < 0.05). A steady vasoconstriction was only obtained at the highest dose of 5-HT. Ketanserin induced a dose-dependent increase in forearm blood flow from 15 ng/kg/min (p < 0.05) onward. The vasodilatation induced by 5-HT (1 ng/kg/min) was significantly enhanced by ketanserin (125 ng/kg/min; p < 0.05), whereas the vasoconstriction elicited by 5-HT (80 ng/kg/min) was reversed by ketanserin (50 ng/kg/min; p < 0.05), thus confirming that 5-HT2receptors were stimulated by 5-HT. In this model ketanserin proved to be a more potent antagonist of aradrenergic receptors than of 5-HT2receptors, since the vasoconstriction induced by methoxamine and tyramine was reduced by a lower dose of ketanserin than was the vasoconstriction induced by 5-HT. It is concluded that 5-HT acts predominantly as a vasodilator in healthy subjects, probably by 5-HT1-like receptor stimulation. Only at high doses of 5-HT did vasoconstriction mediated by 5-HT2receptor stimulation occur. The vasodilatation induced by ketanserin was due most likely to its aradrenergic blocking properties.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

The present study was designed to investigate whether non-insulin-dependent diabetic hypertensive patients exhibit abnormalities in intracellular sodium metabolism similar to those described for essential hypertensive patients. Both normotensive and hypertensive non-insulin-dependent diabetic patients had similar average values of both Na+-Li+ countertransport and Na+-K+ cotransport compared with nondiabetic controls. Within the group of diabetic patients, hypertensive patients did not exhibit any abnormalities in either of the sodium transport pathways studied. The possible implications of these findings are addressed.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID

摘要:

Both the standard mercury sphygmomanometer and the random-zero sphygmomanometer have been used in epidemiological studies and clinical trials. Problems arise in comparing studies since, in addition to other methodological differences, the readings obtained with the randomzero sphygmomanometer have been found to be lower than those obtained with the standard mercury sphygmomanometer. In the present study, blood pressures were measured in 66 subjects to examine the comparability of findings with the two instruments. Trained observers measured blood pressures simultaneously using a double-headed stethoscope and one cuff connected to the two sphygmomanometers. Use of instrument was randomly assigned for each blood pressure measurement; each observer was unaware of the other's blood pressure reading. Readings were lower with the random-zero sphygmomanometer; mean difference ranged from 2.5 to 3.3 mm Hg for systolic pressure and 1.9 to 2.7 mm Hg for diastolic pressure. Digit distributions recorded by the two observers for the standard mercury sphygmomanometer and the random-zero sphygmomanometer were not significantly different for either systolic or diastolic blood pressure. Intraindividual variation was greater with the random-zero sphygmomanometer than with the standard mercury sphygmomanometer. These data do not indicate that one instrument is clearly superior to the other, although in studies where the observer seeks to reduce the bias of multiple readings per person, the random-zero sphygmomanometer may be the more appropriate instrument. Critical to the use of either instrument are careful training, standardization, certification, and periodic recertification of observers.

ISSN:0194-911X    

出版商:OVID    

年代:1988

数据来源: OVID