ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

In a randomized, parallel, double-blind study, lisinopril (n=412; average dose 18.8mg) reduced systolic and diastolic blood pressure (change=20.2/13.8mmHg;P<0.01/PP <0.01) more than nifedipine (n=416; average dose 37.4mg; change=13.3 /11.2 mmHg) after 10-week treatment in patients, aged 40-70 years, with mild-tomoderate essential hypertension. Lisinopril was better tolerated than nifedipine. The withdrawals from treatment were fewer in the lisinopril-treated group (11 versus 46;P<0.01). The frequency of adverse experiences reported after a general question of discomfort was significantly lower for lisinopril than for nifedipine (11 versus 46;P<0.01). When questioned on specific symptoms, frequency of coughing was higher with lisinopril (P<0.01), while flushing, edema, palpitations, dizziness, tiredness and rash were reported more frequently (P<0.01, for all) in the nifedipine-treated group. Quality of life was assessed by both patients and spouses. No significant changes in wellbeing were observed for either drug, except for the highest dose level of nifedipine which caused a deterioration

ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Malignant stroke-prone spontaneously hypertensive rats (M-SHRSP) are a useful animal model for studying juvenile malignant hypertension. Using M-SHRSP males, the effects of SQ 29,852 { (S)-1-[6-amino-2-[[hydroxy (4-phenylbutyl) phosphinyl]oxy]-1-oxohexyl]- proline; 30-40 mg/kg per day}, captopril (30-40 mg/kg per day), hydralazine hydrochloride (10-15 mg/kg per day) and a 33% fish meal diet on the prevention and therapy of malignant hypertension were examined. Drugs and diet were given separately, beginning at weaning, maturity or adulthood. Observed effects included antihypertension, prolonged life span and prevention and/or reversal of angionecrosis. Each treatment resulted in an antihypertensive effect, but some adult rats seemed treatment-resistant. SQ 29,852 was the most effective treatment for reducing blood pressure. The life span of animals in the treated groups was extended significantly beyond that of the controls. In particular, those rats treated with either captopril or SQ 29,852 lived in excess of 500 days. This included not only those in which treatment resulted in a lowering of blood pressure, but also those whose severe hypertension was not so reduced. Angionecrosis was observed in the organs of many of the non-treated animals, including the brain, heart, kidneys and testes. Both hydralazine and the fish meal diet had a limited effect, if any, on the prevention or reversal of angionecrosis. In contrast, almost none of the rats given either captopril or SQ 29,852 showed cerebrovascular lesions or angionecrosis of the brain, heart and kidneys; angionecrosis in adult M-SHRSP kidneys disappeared within 10 or 18 days after the initiation of SQ 29,852 or captopril, respectively. This data seems to support a possible role for these two drugs not only in prevention, but also in repair, of angionecrosis independent of markedly high blood pressure in M-SHRSP. Based on our overall observations, SQ 29,852 was seen as the most effective of the treatments studied

ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We investigated the effects of the human renin inhibitor, ES-8891, and captopril on renal renin secretion and storage in the marmoset. Either ES-8891 (30mg/kg) or captopril (2 mg/kg) was given orally twice a day for 1 week to conscious, sodium-depleted marmosets (n=6 for each group). The ES-8891-treated group displayed a significant reduction in mean arterial pressure (MAP), plasma renin activity (PRA) and plasma immunoreactive renin (PIR) compared with the control group. Kidney renin content was significantly increased compared with the control group and enlarged renin granules containing heterogenous internum were observed in juxtaglomerular cells after treatment with ES-8891. Treatment with captopril significantly increased PRA and PIR compared with the control day as well as increasing kidney renin content and the number of renin granules with crystalline content in juxtaglomerular cells compared with the control group. These results suggest that ES-8891 inhibits both PRA and renin secretion from the kidney, resulting in an increase in renal renin storage

ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Studies of the baroreceptor heart rate reflex were performed in two-kidney, one clip (2K1C) hypertensive rats to evaluate the relative importance of two factors — high blood pressure and high angiotensin II circulating levels — on impairment of the baroreflex, present in the acute phase of this model of hypertension. The sensitivity of baroreceptor reflex was determined by the slope of the relationship between changes in mean arterial pressure (MAP) and changes in heart rate in response to injections of phenylephrine and nitroprusside. Bradycardic and tachycardic responses were analyzed separately. In basal conditions, the slope of the MAP-heart rate relationship in 2K1C hypertensive animals was significantly lower than in control animals, both for tachycardic and bradycardic responses. Lowering of blood pressure with captopril to normotensive levels in the 2K1C animals significantly increased baroreflex gain in bradycardic responses to the level found in normotensive rats. Normalization of blood pressure with nitroprusside did not change baroreflex sensitivity. Infusion of angiotensin II at a dose that did not change MAP, previously normalized with captopril, completely reverted the effect of this agent on baroreflex sensitivity. Our data indicate that, in 2K1C hypertensive rats, decreased baroreflex sensitivity is mediated, at least in part, by high angiotensin II circulating levels. Elevated blood pressureper seis of secondary importance

ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

This study investigated whether fractional lithium excretion (FELi), used as a marker of proximal fluid delivery, changes during different phases of essential hypertension. Forty-eight subjects were studied: 12 essential hypertensives (EH); 12 borderline hypertensives (BL); 12 normotensives with a positive family history of essential hypertension (NH) and 12 normotensives without a family history of essential hypertension (NN). Measurements were performed in the recumbent position, both in basal conditions and after a saline load (2% body weight in 1 h; 0.333 ml/min per kg body weight). In basal conditions, a moderate extracellular volume expansion was already present in the subjects. In these conditions, FELiof EH was significantly higher than that of all the other groups (P<0.01). After the saline load, fractional sodium excretion increased in all the groups (P<0.01), but to a significantly greater extent in EH (P<0.01). FELirose significantly only in BL (P<0.05). The change in FELIof BL correlated positively (P<0.02) with the change in blood pressure in 10 of these subjects 3 years after this study. Moderate extracellular volume expansion may be able to either reveal or stimulate an increase of FELiin subjects with established hypertension. When a greater degree of extracellular volume expansion is induced, this increases FELiin BL and this effect may be related to the subsequent development of hypertension

ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

Experiments were performed in anaesthetized dogs to characterize the renal effects of the selective dopamine DA1-receptor agonist, fenoldopam. Intrarenal artery infusion of fenoldopam (0.01-10µg/kg per min) caused dose-related renal vasodilation. At low doses (0.01-0.3 µg/kg per min), renal vasodilation occurred without concomitant falls in blood pressure but was accompanied by increased urine output. This diuresis was most probably a result of reduced tubular reabsorption since glomerular filtration rate was not increased. Both fenoldopam-induced renal vasodilation and diuresis were blocked to a similar extent by the selective dopamine DA1-receptor antagonist, SCH 23390 (30µg/kg, intravenously), suggesting that both effects were mediated by dopamine DA1-receptors. In the presence of the angiotensin converting enzyme inhibitor, captopril (1 mg/kg, intravenously, + 20 µg/kg per min, intrarenal artery), fenoldopam (0.01-0.3µg/kg per min) significantly increased fractional excretion of sodium, despite reducing blood pressure; neither of these effects were observed in captopril-free dogs. These observations support the view that the inhibitory effect of fenoldopam on tubular function, and its vasodepressor activity, may be opposed by angiotensin II resulting from fenoldopam-induced renin release

ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We have previously reported that pressor doses of angiotensin II induce atrial natriuretic factor (ANF) release. Since the number of glomerular and vascular ANF receptors may vary inversely with plasma ANF levels, we investigated whether they are modified by angiotensin II. Male rats were infused intraperitoneally for 7 days with either a non-pressor (200ng/kg per min) or a pressor (800 ng/kg per min) dose of angiotensin II. Sham-infused animals served as controls. Blood pressure and plasma C- and N-terminal ANF were higher, and atrial ANF concentrations lower, in pressor than in either non-pressor or sham-infused groups. Glomerular ANF receptor density was lower in pressor than in either non-pressor or sham-infused animals. The production of cyclic guanosine monophosphate by isolated glomeruli was significantly lower in pressor than in either non-pressor or sham-infused groups. Vascular ANF receptor density was lower in pressor than in either sham-infused or non-pressor rats. No difference in affinity was observed in any group for either glomerular or vascular ANF receptors. Neither the density nor the affinity of glomerular and vascular ANF receptors were affected by prior washing of the membranes with an acid solution (pH 5.0). Irreversible cross-linking of125l-ANF followed by sodium dodecylsulfate-polyacrylamide gel electrophoresis in reducing conditions and autoradiography demonstrated that both high- and low-molecular weight receptors were downregulated in glomerular membranes, but only the low-molecular weight receptor was reduced in vascular membranes after a high-dose infusion of angiotensin II. We conclude that angiotensin II induces a true downregulation of its glomerular and vascular receptor subtypes, probably by increasing plasma ANF levels. A direct or indirect effect of angiotensin II on ANF receptor regulation cannot be eliminated, however

ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

By using aortic adventitial fibroblasts in culture as a model, we first demonstrated that cells derived from spontaneously hypertensive rats (SHR), when compared with Wistar-Kyoto (WKY)-derived cells, possessed an increased capacity to proliferate and to synthesize DNA in response to vasoactive agents. At this early stage of culture, SHR fibroblasts exhibited a higher specific growth rate. Then, to gain insight into the mechanisms which could be responsible for the difference observed, signalling pathways involved in the transduction of the mitogenic signal were analysed in cells cultured for 3 days. Results indicated that, in SHR-derived fibroblasts, an increased phospholipase C activity could account for the higher mitogenic response to thrombin or vasopressin. However, this enzymatic activity, which did not differ when fibroblasts from the two rat strains were stimulated by serum, could not be responsible for the enhanced proliferation rate of SHR-derived cells. Moreover, neither protein kinase C nor pertussis toxin-sensitive C proteins appeared to contribute to the hyperresponsiveness exhibited by SHR fibroblasts. Our results indicate that the mechanism(s) responsible for such a difference vary according to the stimulus; they also suggest that adventitial fibroblasts may participate in the modified reactivity of vascular wall associated with hypertension

ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID

摘要:

We compared the ability of a high-NaCl diet to produce blood pressure elevation in spontaneously hypertensive rats (SHR) from the major North American commercial suppliers (Harlan, Taconic Farms, Charles River) and SHR and stroke-prone SHR (SHRSP) from the National Institutes of Health (NIH). Animals were raised on a low-NaCl diet containing 0.30% NaCI and placed on an 8.0% NaCl diet at 37 days of age. In males, the high-NaCl diet produced large increments in blood pressure within 2-4 weeks, which were similar in magnitude for all SHR derivations. In females, increments in blood pressure occurred more slowly than in males but, in most SHR derivations, the absolute blood pressure level eventually reached was similar to that seen in males. The present findings provide no evidence of sub-line differentiation among SHR stocks from the United States regarding the blood pressure-augmenting effects of increased levels of NaCI and are consistent with the results of DNA fingerprinting studies, which have not found any genetic variation between SHR from different colonies. We speculate that the pervasive gender differences in the blood pressure response to the high-NaCl diet in SHR may reflect gender differences in food intake, and hence the dose of NaCl received, rather than intrinsic differences between males and females. On the other hand, the lack of significant gender differences in blood pressure response to the high-NaCl diet in SHRSP may reflect the genetic differences which are known to exist between this strain and the main SHR stemline

ISSN:0263-6352    

出版商:OVID    

年代:1991

数据来源: OVID