ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID

ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

In recent years, the ability of the various antihypertensive drugs to provide renal protection has been the subject of increased attention. Whether calcium antagonists prevent or reduce the rate of progression of renal damage is still a matter of controversy. This paper reviews the findings of recent animal and human studies on the haemodynamic and renal protective effects of calcium antagonists. These agents preferentially vasodilate afferent arterioles, leading to an increase in renal blood flow and glomerular filtration rate. These effects are more pronounced in hypertensive patients than in normotensive subjects and persist even when renal function is impaired. In animal models of chronic renal failure, calcium antagonists can reduce glomerulosclerosis. However, the mechanisms involved in their renal protective effect appear to be different from those of angiotensin converting enzyme (ACE) inhibitors as they do not reduce intraglomerular pressure. Renal failure caused by vasoconstriction related to radiocontrast agents or cyclosporine can be partly prevented by the administration of a calcium antagonist. Furthermore, in patients with renal artery stenosis, calcium antagonists reduce blood pressure with less renal blood flow impairment than ACE inhibitors. Preliminary clinical studies suggest that verapamil or diltiazem may reduce proteinuria in hypertensive diabetic patients. Whether these compounds can also retard the progression of renal failure in these patients remains to be established with larger trials.

ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo determine ambulatory and home blood pressure means and distributions in relation to clinic blood pressure in a general population.MethodsWe obtained a random sample of 2400 subjects stratified by sex and 10 year age groups to be representative of residents aged 25–64 years of the city of Monza. Participation rate was 69% (1651 subjects). Blood pressure measurements consisted of clinic blood pressure (average of three measurements, sphygmomanometry), home blood pressure (average of morning and evening measurements, semiautomatic device) and ambulatory blood pressure (automatic readings at 20 min intervals, Space labs 90207). Clinic blood pressure was obtained both before and after home and ambulatory blood pressures. Data analysis did not include 213 subjects receiving antihypertensive drug treatment and was therefore limited to 1438 participants. Results: In the 1438 subjects, clinic, home and ambulatory blood pressure showed a normal-like distribution, with a taller peak and a narrower base for ambulatory than for home and clinic values. Clinic, home and ambulatory blood pressures were significantly related to each other (Palways < 0.001). The means of the two clinic blood pressures obtained on consecutive days were superimposable (127.4 ± 17.0/82.3 ± 9.8 and 128.2 ± 16.5/81.9 ± 9.9 mmHg) and both were markedly higher than home and 24 h average blood pressures (8.2 mmHg), which were similar to one another. The differences between clinic and home or 24 h average blood pressure were similar in both sexes but increased with increasing age and clinic blood pressure values. The influence of clinic blood pressure values on the clinic-ambulatory or clinic–home blood pressure differences was more important than age. Although higher than the 24 h average value, daytime average blood pressure was also lower than clinic blood pressure. Night-time blood pressure was markedly lower than the daytime value in both sexes and at all ages.ConclusionData from a large and unbiased sample of a general population show that home and 24 h or daytime average blood pressures are much lower than clinic blood pressure. The relatively close correlation between blood pressure values measured with the different methods used has allowed calculation of home and ambulatory blood pressure values corresponding to the accepted upper limit of normality of clinic blood pressure (140/90 mmHg). The upper limit of normality for the population was for both home and ambulatory blood pressures in the range 120–130 and 75–81 mmHg for systolic and diastolic values, respectively, with slight differences depending on sex and age. Taking 140/90 mmHg as the upper normal limit of the population is therefore an error that leads to individuals whose home or ambulatory blood pressures are high being considered as normotensive.

ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveDaily exposure to air-jet stress (AJS) causes sustained elevations of blood pressure in borderline hypertensive rats (BHR). It is known that the renin–angiotensin system is activated during episodes of behavioral stress, and the purpose of this study was to assess the involvement of renin–angiotensin system in the development of stress-induced hypertension in the BHR.DesignFour groups of 8− and 9-week-old rats were studied: they received, respectively, oral captoprii and AJS; oral captopril without AJS; AJS without captopril; and neither AJS nor captopril.MethodsAfter 10 days of AJS and captopril conditions, femora! and jugular catheters were implanted for the measurement of mean arterial pressure and pressor responses to norepinephrine and tyramine. Blood samples were collected for the measurement of norepinephrine and plasma renin activity.ResultsTen days of AJS caused a significant elevation of blood pressure in BHR exposed to AJS without receiving captopril but not in those animals given captopril concurrently with AJS. Circulating norepinephrine and blood pressure responses to exogenous norepinephrine and tyramine were similar across the four groups. Plasma renin activity was highest in BHR given captopril, and was significantly elevated during an acute episode of AJS.ConclusionsThe renin–angiotensin system may be important in the development of stress-induced hypertension in the BHR.

ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveIn the present study we tested the hypothesis of whether the centrally induced natriuresis and blood pressure increase after intracerebroventricular injection of hypertonic saline involves the subfornical organ, as suggested by the occurrence of osmosensitive cells as wellas a high concentration of angiotensin II receptors in this brain area.MethodsAll experiments were performed in conscious Wistar rats. A chronic cannula was inserted into the lateral brain ventricle for intracerebroventricular injection and a chronic indwelling intracranial guide cannula for microinjection was placed in the subfornical organ. In addition, the rats were provided with ureter catheters for urine collection.ResultsIntracerebroventricular injections of hypertonic saline (0.3 mol/l; n = 7) increased renal sodium excretion from 180.0 ± 30.0 to 279.0 ± 34.0 mol/l/60 min (P< 0.001) accompanied by an increase in mean arterial pressure of 8.3 ± 1.2 mmHg (P< 0.01). No change in urinary volume was observed. After injection of the specific AT1receptor antagonist, losartan, into the subfornical organ (5 μg/200 nl; n = 8) the natriuresis and blood pressure response to intracerebroventricular hypertonic saline was completely abolished. Control injections of losartan into areas adjacent to the subfornical organ had no effect on the responses to hypertonic saline. Conclusion: Our results suggest that the centrally induced natriuresis and blood pressure responses to hypertonic saline are mediated by an angiotensinergic mechanism involving the subfornical organ.

ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo study the different cardiac and renal hemodynamic effects of an angiotensin converting enzyme inhibitor and an angiotensin II receptor antagonist in experimental heart failure in conscious dogs.Design and methods: We compared the effects of the angiotensin converting enzyme inhibitor, captopril, with those of the angiotensin II (Ang II) subtype-1 receptor antagonist, losartan, on hemodynamics and hormonal changes in congestive heart failure by rapid ventricular pacing on conscious dogs. Furthermore, we characterized the Ang II receptors in canine heart, using the canine cardiac membrane fraction in heart failure.ResultsAcute intravenous administration of captopril improved the cardiac output by 19% (P< 0.01) but losartan did not, although blockade of the renin–angiotensin system by losartan (1.1 μmol/kg) or captopril (0.69 μmol/kg) induced similar changes in the plasma renin activity, norepinephrine and arginine vasopressin, and a similar decrease in mean arteriaI pressure (–10 mmHg). Renal blood flow was increased by either losartan or captopril. In the binding study, losartan produced a single displacement curve (IC550= 0.25 μmol/l), while the Ang II subtype-2 (AT2) receptor antagonist PD123319 did not, indicating that the predominant Ang II receptor is type-1 (AT1) in canine heart. Neither the ratio of AT1to AT2receptors nor the receptor density changed with the development of heart failure.ConclusionsThe lack of effect of losartan on cardiac output may be the result of its inability to block non-AT1receptor-mediated Ang II activities adequately. Captopril may improve cardiac output by means of mechanisms not mediated by Ang II, such as locally increasing bradykinin.

ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo probe the potential influence of a high renal tubular level of angiotensin II on sodium reabsorption using angiotensin converting enzyme inhibitors and a non-peptide angiotensin antagonist.MethodsSystemic arterial blood pressure, renal blood flow (RBF) and electrolyte and urinary excretion were measured in anesthetized uninephrectomized Wistar rats. Captopril (n = 12), ramiprilat (n = 10) or EXP 3174 (n = 9) was infused into the renal artery in graded doses to examine whether the threshold dose that increased RBF was lower than that which increased sodium excretion rate (Na+excretion rate). Results: Whereas ramiprilat (0.5–4 μg/kg/min intra-arterially) and EXP 3174 (0.5–4 μg/kg/min intra-arterially) decreased blood pressure in all but the lowest dose of 0.5 μg/kg/min, captopril (1–8 μg/kg/min intra–arterially) did not change blood pressure except for a slight effect with the two higher doses. These three agents increased RBF to about the same degree, between 6% and 18%, which was relatively large compared with the maximal vasodilator response achievable in the kidney with acetylcholine (30–37%). Captopril given intra–arterially had a more consistent effect on Na+excretion rate than either ramiprilat or EXP 3174. An increase in Na+excretion rate occurred with captopril ranging from 44% to 78%, whereas no significant change was obtained with the other drugs. The dose of captopril that increased RBF was the same as that which increased Na+excretion rate. In those experiments in which ramiprilat resulted in an increase in Na+excretion rate (five of 10 experiments), the effective dose was the same as that which increased RBF.ConclusionWhen administered by the intra-arterial route, captopril was more effective in increasing Na+excretion rate than either ramiprilat EXP 3174. Although the threshold dose of captopril and ramiprilat required to increase Na+excretion rate and RBF was similar, suggesting blockade of a common angiotensin II pool, there was not a good correlation between these two effects.

ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

ObjectiveTo compare fibroblast populations derived from spontaneously hypertensive rats (SHRLJ) and normotensive Wistar–Kyoto rats (WKYLJ) for angiotensin II receptor binding, gene expression of the AT1receptor and angiotensinogen, hormone responsiveness and phenotypic changes.MethodsFibroblasts were isolated by either collagenase B or collagenase P and grown to confluency in the presence of 10% fetal bovine serum. Angiotensin II receptor binding was assessed under both serum and serum-free conditions. Hormonal treatment of cells was conducted in a serum-free background. The concentrations of AT1receptor and angiotensinogen messenger RNA (mRNA) were determined by liquid hybridization. Phenotypic changes in fibroblast populations were analysed by visualization of lipid-containing vacuoles (oil red O stain) or of α-smooth muscle actin-containing fibres (immunostain).ResultsSHRLJcollagenase-B cells grew more slowly and had nearly twofold fewer angiotensin II receptors than WKYLJcells as measured by both radioligand binding and AT1mRNA content (SHRLJ1.34 ± 0.05 versus WKYLJ, 5.94 ± 0.41 pg mRNA per μg total RNA) but contained significantly more angiotensinogen mRNA (SHRLJ147 ± 12 versus WKYLJ98 %% 8 fg mRNA per μg total RNA). Collagenase-P cells from the two strains exhibited similar binding and growth properties. Collagenase-B fibroblasts also exhibited greater responses to exogenous steroids, including a greater shift towards an adipocyte phenotype, than collagenase-P cells. Exogenous angiotensin II promoted transformation towards a myofibroblast cell type, especially in collagenase-P SHRLJcells.ConclusionOur results indicate that subsets of fibroblasts that differ in growth rate, angiotensin II receptor binding, AT1and angiotensinogen mRNA levels, structure and steroid responsiveness may be isolated from the left ventricle. The potential importance of these altered phenotypes to cardiac remodelling and hypertrophy warrants further examination.

ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID

摘要:

Objectiveto evaluate the effect of dietary potassium on blood pressure and vascular contractility in adult rats of two strains, spontaneously hypertensive rats (SHR) and normotensive Wistar–Kyoto (WKY) rats.Design‘Potassium-induced relaxation’ was evaluated in aortic rings as a functional measure of Na,K-ATPase activity in the vascular wall. The rats were fed one of three diets: regular (American Institute of Nutrition-76 rat chow); high-sodium (7% sodium chloride) or high-sodium plus potassium (7% sodium chloride and 13.4% potassium citrate) for 12 ± 1 weeks.ResultsSHR fed the high-sodium diet had a mean blood pressure of 157 ± 8 mmHg, as compared with 130 ± 9 mmHg for those on a regular diet (P< 0.01). SHR fed the potassium-supplemented diet had a blood pressure of 122 ± 9 mmHg (P< 0.01 versus the high-sodium diet group). The mean blood pressure of WKY rats was 78 ± 3 mmHg and did not differ among the dietary groups. The ‘potassium-induced relaxation’ response of aortic rings from SHR and WKY rats fed a potassium-supplemented diet was significantly higher (P< 0.05) than that in animals in the corresponding high-sodium dietary group. This observation in potassium-supplemented rats is interpreted as indicative of increased Na,K-ATPase activity in the vascular wall. Conclusions: A potassium-rich diet in SHR receiving a high sodium intake was associated with lower blood pressure and higher vascular Na,K-ATPase activity. A similar effect of this diet on vascular Na,K-ATPase was observed in WKY. We propose that the antihypertensive effect of a potassium-rich diet is mediated, at least in part, by stimulation of vascular Na,K-ATPase activity.

ISSN:0263-6352    

出版商:OVID    

年代:1995

数据来源: OVID