摘要:

We have previously reported that high dietary salt exposure significantly increases daytime mean arterial pressure in spontaneously hypertensive rats (SHR) but not in normotensive Wistar-Kyoto (WKY) controls. In the present study, we used a telemetry monitoring system to evaluate the effects of high dietary salt exposure on diurnal variation of mean arterial pressure and heart rate in SHR and WKY rats. After implantation of a radio frequency transducer, SHR and WKY rats were maintained on either high (8%) or basal (1%) salt diets. Hemodynamic values were then analyzed for diurnal variation with the use of a nonlinear data-fitting program. After 2 weeks of dietary exposure, high salt–fed SHR had significantly greater 24-hour mean arterial pressure (156±3 mm Hg) than SHR receiving basal (135±2 mm Hg) and WKY rats receiving high (100±2 mm Hg) or basal (100±1 mm Hg) salt diets. Rhythm analysis indicated significant increases in both daytime and nighttime mean arterial pressure during high salt exposure in SHR. In WKY rats, high salt exposure increased nighttime but not daytime mean arterial pressure, with no net effect on 24-hour mean arterial pressure. High dietary salt exposure significantly decreased heart rate in both SHR and WKY rats, and it did not significantly alter the pattern of diurnal blood pressure or heart rate variation. These results indicate that WKY rats manifest an acute sensitivity to salt ingestion but have compensatory mechanisms sufficient to prevent sustained increases in mean arterial pressure; such mechanisms are lacking in SHR.

ISSN:0194-911X    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Vascular smooth muscle cells isolated from spontaneously hypertensive rats (SHR) replicate faster in vitro than do cells from Wistar-Kyoto (WKY) rats, suggesting that the vascular hypertrophy seen early in the life of SHR might be at least partially caused by abnormal cellular growth properties in vivo. To test whether specific growth stimuli produce more extensive hypertrophy in SHR than WKY rats, we compared their cardiovascular growth responses to two-kidney, one clip renal hypertension. Six-week-old animals were subjected to either renal artery clipping or sham operation. Four weeks after renal artery clipping, there was a proportionately smaller rise in systolic blood pressure in SHR than WKY rats (21% and 44%, respectively); however, the overall level of systolic blood pressure achieved in the two rat strains differed by less than 10 mm Hg (4%). Limitations in the blood pressure responses of SHR to renal artery clipping were not due to inadequate development of left ventricular hypertrophy, as this was greater in SHR than WKY rats; however, aortic hypertrophy was similar in both strains. Aortic DNA content changes in SHR were consistent with a significant hyperplasia of medial smooth muscle cells, whereas in WKY rats, there was cellular hypertrophy. Small and medium-sized arteries of the mesenteric vasculature were also hypertrophied in SHR, and the medial cross-sectional area increased by 63% and 114%, respectively, compared with increases of only 15% and 23% in WKY rats. Strain differences between the shamoperated rat groups were small. In a hemodynamic analysis of the hindquarter vasculature performed under constant flow conditions, an increase in vascular resistance was consistent with encroachment of the vessel wall on the lumen. Average hindquarter vascular lumen diameter appeared smaller in SHR than WKY rats, and the increase in perfusion pressures during maximal constriction with methoxamine plus angiotensin II in both rat strains also suggested significant vessel wall hypertrophy. The increase in perfusion pressure at maximal constriction was greater in SHR than WKY rats, and the absolute level of systolic blood pressure could not account for this difference. Overall, this study indicates that the cardiovascular system of the SHR is more responsive to the hypertrophic stimuli of two-kidney, one clip renal hypertension. The more rapid and in some vessels more extensive hypertrophy that develops in SHR compared with WKY rats, despite only small differences in systolic blood pressure, supports the hypothesis that the stimulation of genes that contribute to the abnormal growth of vascular smooth muscle cells of the SHR may contribute to the development of vascular hypertrophy in these animals.

ISSN:0194-911X    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

To simulate in vivo conditions as closely as possible to in vitro conditions, we examined the morphological and functional characteristics of isolated human subcutaneous small arteries from 17 essential hypertensive patients and 14 normotensive control subjects using a perfusion myograph. Vessel segments were cannulated and exposed to conditions of constant flow and pressure. The ratio of media thickness to lumen diameter in arteries from hypertensive patients increased significantly. With the endothelium intact, sensitivity to extraluminally applied norepinephrine was not different, and this was not affected by inhibition of neuronal amine uptake with cocaine. After removal of the endothelium, sensitivity to norepinephrine was augmented in normotensive vessels to a greater extent than in hypertensive vessels. Endothelium-dependent relaxation to acetylcholine was significantly reduced in arteries from hypertensive patients, but endothelium-independent relaxation to sodium nitroprusside was not different from that observed in vessels from normotensive control subjects. These data demonstrate that sensitivity to exogenous norepinephrine is not different in essential hypertension but that there is defective endothelium-dependent dilatation, suggesting a contributory role for endothelium dysfunction in human essential hypertension.

ISSN:0194-911X    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

In response to hypertension, arterioles remodel their structure, the heart develops myocardial hypertrophy, and the kidney reduces creatinine clearance and increases albuminuria. To better understand the interrelations among the target organs involved in hypertension, we evaluated minimal forearm vascular resistances–a hemodynamic index of arteriolar structure derived from mean blood pressure and maximal postischemic forearm blood flow –the echocardiographic indexes of cardiac structure, and urinary albumin excretion and creatinine clearance in 29 male mild to moderate non-macroalbuminuric essential hypertensive patients on no drugs and 11 age- and sex-matched normotensive control subjects. Minimal forearm resistances were elevated in hypertensive patients and correlated with left ventricular mass, wall thickness, and mean arterial pressure. Patients with abnormal minimal forearm resistances (2 SD above normal) were characterized by higher pressure, greater wall thickness, lower creatinine clearance, and higher albumin excretion, suggesting that maximal forearm flow capacity does relate to the hemodynamic load exerted on both the kidney and heart. However, the correlation with cardiac structure and mean arterial pressure explained only part of the variability of minimal forearm resistances. Furthermore, no correlation among these parameters was found when hypertensive patients were evaluated separately from normotensive subjects, possibly because of heterogeneous factors active on arteriolar structure and unrelated to the pressor load. Overall, the data suggest that the development of abnormal minimal forearm resistances in the course of the hypertensive process is related to the pressor load, but its details need further understanding.

ISSN:0194-911X    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

Cardiac fibrosis is one of the deleterious events accompanying hypertension that may be implicated in the progression toward heart failure. To determine the mechanisms involved in fibrosis and the role of hemodynamic versus humoral factors, we studied the expression of genes involved in hypertrophy and fibrosis in the heart of rats treated with aldosterone for 2 months with addition of 1% NaCl and 0.3% KC1 in water. This treatment induced arterial hypertension, a moderate left ventricular hypertrophy, and a decrease in plasma thyroxine. Equatorial sections of hearts from treated rats showed numerous foci of proliferating nonmuscular cells and a biventricular fibrosis. Computerized videodensitometry demonstrated an increase of collagen volume fraction by 152% and 146% and of the ratio of the perivascular collagen area and vascular area by 86% and 167% in left and right ventricles, respectively. As measured by slot blot, this cardiac fibrosis was accompanied by an increase in α1-I procollagen mRNA by 75% and 160% (P<.01) and in α1-III mRNA by 76% and 319% (P<.01) in left and right ventricles, respectively. Atrial natriuretic peptide mRNA was induced only in the hypertrophied left ventricle. We conclude that fibrosis is occurring and involves pretranslational regulation of collagen synthesis. Whereas hypertrophy and atrial natriuretic peptide mRNA increase are restricted to the left ventricle, fibrosis is initiated in both ventricles, supporting the hypothesis that this cardiac response is independent of hemodynamic factors.

ISSN:0194-911X    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The existence of a cardiac renin-angiotensin system, independent of the circulating renin-angiotensin system, is still controversial. We compared the tissue levels of reninangiotensin system components in the heart with the levels in blood plasma in healthy pigs and 30 hours after nephrectomy. Angiotensin I (Ang I)–generating activity of cardiac tissue was identified as renin by its inhibition with a specific active site–directed renin inhibitor. We took precautions to prevent the ex vivo generation and breakdown of cardiac angiotensins and made appropriate corrections for any losses of intact Ang I and II during extraction and assay. Tissue levels of renin (n=11) and Ang I (n=7) and II (n=7) in the left and right atria were higher than in the corresponding ventricles (P<.05). Cardiac renin and Ang I levels (expressed per gram wet weight) were similar to the plasma levels, and Ang II in cardiac tissue was higher than in plasma (P<.05). The presence of these renin-angiotensin system components in cardiac tissue therefore cannot be accounted for by trapped plasma or simple diffusion from plasma into the interstitial fluid. Angiotensinogen levels (n=11) in cardiac tissue were 10% to 25% of the levels in plasma, which is compatible with its diffusion from plasma into the interstitium. Like angiotensin-converting enzyme, renin was enriched in a purified cardiac membrane fraction prepared from left ventricular tissue, as compared with crude homogenate, and 12±3% (mean±SD, n=6) of renin in crude homogenate was found in the cardiac membrane fraction and could be solubilized with 1% Triton X-100. Tissue levels of renin and Ang I and II in the atria and ventricles were directly correlated with plasma levels (P<.05), and in both tissue and plasma the levels were undetectably low after nephrectomy. We conclude that most if not all renin in cardiac tissue originates from the kidney. Results support the contentions that in the healthy heart, angiotensin production depends on plasma-derived renin and that plasma-derived angiotensinogen in the interstitial fluid is a potential source of cardiac angiotensins. Binding of renin to cardiac membranes may be part of a mechanism by which renin is taken up from plasma.

ISSN:0194-911X    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The regional hemodynamic effects of 5 days of intravenous infusion of corticotropin (ACTH) (5 μg/kg per day) were examined in conscious sheep (n=8). Mean arterial pressure increased from 81±2 to 93±3 mm Hg (P<.001) on day 2 of ACTH and remained at this level during the infusion. Cardiac output increased from 5.13±0.19 to 6.06±0.33 L/min (P<.O1) because of an increase in stroke volume from 65±4 to 79±8 mL per beat (P<.01); heart rate remained unchanged. ACTH did not alter total peripheral conductance but had differential effects on regional conductances. Mesenteric conductance fell from 5.8±0.2 to a minimum of 4.9±0.3 (mL/min)/mm Hg (P<.05), and renal conductance increased from 3.5±0.3 to 4.6±0.3 (mL/min)/ mm Hg (P<.001). There was a small increase in iliac conductance (P<.05) and no change in coronary conductance. Mesenteric and iliac conductances fell progressively over 24 to 48 hours, whereas renal conductance increased rapidly after 3 hours of ACTH, reaching a maximum after 6 hours. Renal blood flow was increased during ACTH infusion from 278±18 to 403±23 mL/min (P<.001); mesenteric blood flow was unchanged; there was a small increase in iliac blood flow (P<.01); and coronary blood flow increased (P<.05), paralleling the change in cardiac output. In a further five sheep, ACTH (5 μg/kg per day) increased mean arterial pressure by 17±2 mm Hg and central venous pressure by a maximum of 5.3±0.8 mm Hg. Plasma atrial natriuretic peptide concentration increased from 12.4±6.2 to 98.0±25.8 pg/mL (P<.01), but plasma endothelin concentration remained unchanged. In summary, ACTH had diverse regional hemodynamic actions, causing mesenteric vasoconstriction and renal vasodilation, with little effect on the coronary and iliac circulations. The pressor effect of ACTH resulted from the increase in cardiac output together with mesenteric vasoconstriction, which offset the renal vasodilation, resulting in no change in total peripheral conductance.

ISSN:0194-911X    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

The outcome of 1999 apparently healthy men aged 40 to 59 years investigated from 1972 through 1975 was ascertained after 16 years to determine whether systolic blood pressure measured with subjects in the sitting position during a bicycle ergometer exercise test adds prognostic information on cardiovascular mortality beyond that of casual blood pressure measured after 5 minutes of supine rest. During a total follow-up of 31 984 patient years, 278 patients died, 150 from cardiovascular causes. Casual blood pressure and pulse pressure as well as peak exercise systolic blood pressure during 6 minutes on the starting workload of 600 kpm/min (approximately 100 W, 5880 J/min) were all related to cardiovascular mortality. The relative risk (RR) of dying from cardiovascular causes associated with an increment of 48.5 mm Hg (=2 SD) in systolic blood pressure at 600 kilopondmeter (kpm)/min was significant (RR=1.5, 95% confidence interval [CI] = 1.1-2.3,P=.040) even when adjusting for a large number of variables measured in the present study, including age, exercise capacity, smoking habits, and casual blood pressures. The influence of blood pressure at 600 kpm/min was so strong that the predictive value of resting casual blood pressures became nonsignificant when these were analyzed as continuous variables also including exercise blood pressure as a covariate. However, the maximal systolic blood pressure during the exercise test was unrelated to cardiovascular mortality. Among the 520 men with resting systolic blood pressure of 140 mm Hg or greater, those 304 who increased their systolic blood pressure to 200 mm Hg or greater during 6 minutes of the starting exercise workload of 600 kpm/min had a 16-year cardiovascular death rate of 16.1% compared with 6.0% among those with a systolic blood pressure less than 200 mm Hg at 600 kpm/min (n=216, RR=2.0, 95% CI=1.1-4.0,P=.025). The cardiovascular death rate was also 6.0% among those who were normotensive at rest (n=1479). Thus, an early rise of systolic blood pressure during exercise adds prognostic information on cardiovascular mortality among otherwise healthy middle-aged men with mildly elevated casual blood pressure.

ISSN:0194-911X    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

We conducted the present study to determine whether the angiotensin II type I receptor (AT1) gene might be implicated in human essential hypertension by using case-control and linkage studies. The entire coding and 3′ untranslated regions of the AT1receptor gene (2.2 kb) were amplified by polymerase chain reaction and submitted to single-strand conformation polymorphism in 60 hypertensive subjects with a familial susceptibility. We identified five polymorphisms (T573→C, A1062→G, A1166→C, G1517→T, and A1878→G). However, no mutations that alter the encoded amino acid sequence were detected. A case-control study performed on white hypertensive (n=206; blood pressure, 168±16/103±9 mm Hg) and normotensive (n=298; blood pressure, 122±10/75±9 mm Hg) subjects using three of five polymorphisms showed a significant increase in allelic frequency of C1166in hypertensive subjects (0.36 versus 0.28 for normotensive subjects, χ2=6.8,P<.01). Frequencies for the alleles of the other two polymorphisms (T573→C, A1878→G) were similar in both groups. We performed a linkage study using the affected sib pair method and a highly polymorphic marker of the AT1receptor gene. There was no evidence for linkage in 267 sib pairs analyzed from 138 pedigrees. These findings would be compatible with a common variant of the AT1receptor imparting a small effect on blood pressure; further studies will be needed to address this possibility.

ISSN:0194-911X    

出版商:OVID    

年代:1994

数据来源: OVID

摘要:

We studied the local renin-angiotensin system in the microcirculation of cremaster muscle in spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto (WKY) controls. We used intravital microscopy in an original preparation of cremaster isolated from its normal blood supply and externally perfused with physiological solution, thus allowing the exclusion of circulating converting enzyme, circulating renin, and circulating angiotensinogen. We classified arterioles studied as second-, third-, and fourth-order, with mean diameters, respectively, of 67±6, 35±2, and 17±1 μn in WKY controls and 61±5, 34±2, and 16±1 μm in SHR. No difference between WKY controls and SHR was found for arteriolar vasoconstrictions in response to topical administration of 0.01 to 1 nmol/mL angiotensin II. Conversely, in response to 0.01 to 1 nmol/mL angiotensin I, significantly more arteriolar vasoconstriction was found in SHR cremaster muscle. In both strains, responses to angiotensin I were significantly inhibited by 10 nmol/mL of the angiotensin-converting enzyme inhibitor lisinopril. When angiotensinogen-rich, renin-free plasma containing 2.3 nmol/mL angiotensinogen was administered, almost no vasoconstriction was found in WKY controls, but significant constrictions were observed in SHR (23±4%, 30±5%, and 41 ±4% for second-, third-, and fourth-order I arterioles, respectively). In SHR, vasoconstriction in response to angiotensinogen-rich, renin-free plasma was dose dependent, was inhibited by lisinopril, and was not found 24 hours after bilateral nephrectomy. Topical administration of 1.2 μg/mL renin did not induce arteriolar vasoconstriction in either WKY or SHR cremaster muscle. We conclude that in the skeletal muscle microcirculation, (1) local angiotensinconverting enzyme activity in arterioles is higher in SHR than in their normotensive controls and is consequently an important target site for angiotensin-converting enzyme inhibitors; (2) the enzymatic cascade constituted by local renin and local angiotensin-converting enzyme is able to produce significant vasoconstriction in the presence of angiotensinogen in SHR but not in their normotensive controls; (3) the bulk of vascular renin responsible for this vasoconstriction in response to angiotensinogen in SHR is likely derived from the uptake of circulating renin of renal origin; and (4) no evidence exists in either WKY rats or SHR for the presence of local angiotensinogen, which can induce arteriolar constriction in the presence of renin.

ISSN:0194-911X    

出版商:OVID    

年代:1994

数据来源: OVID