(1/3311) Altered vascular reactivity following partial nephrectomy in the rat: a possible mechanism of the blood-pressure-lowering effect of heparin.
BACKGROUND: This study was designed to assess whether the antihypertensive effect of heparin in rats after renal mass reduction (RMR) is related to changes in nitric oxide activity, and to study in vitro the altered behaviour of resistance-sized arteries induced by chronic administration of heparin. METHODS: Male Wistar rats were assigned to one of two experimental protocols. In the first protocol, RMR rats received heparin (250 units/day s.c.) and tail systolic blood pressure (SBP) was measured weekly for 4 weeks. In a subgroup, urinary nitrate excretion (UNO3) and in vitro vascular reactivity of isolated perfused mesenteric arterial beds were measured 2 weeks after RMR. The second protocol assessed whether inhibition of NO synthesis with L-NAME (70 mg/l added to the drinking water) prevents the blood-pressure-lowering effect of heparin. RESULTS: In untreated RMR rats SBP increased from 111+/-3 mmHg to 127+/-5 mmHg at 2 weeks and 139+/-5 mmHg at 4 weeks. In contrast, in RMR rats treated with heparin, SBP was 114 +/-3 mmHg at 2 weeks and 115+/-4 mmHg at 4 weeks (P<0.05 for both). Treatment with L-NAME increased SBP both in untreated and heparin-treated RMR groups. Two weeks after nephrectomy daily urinary nitrate increased significantly more in RMR rats treated with heparin than in untreated RMR rats (22+/-2 vs 14.2+/-2.3 micromol/day, P<0.05). In vitro studies performed at 2 weeks showed that vessels of untreated RMR rats had a blunted vasodilator response to acetylcholine that was restored to levels similar to that of controls in the heparin-treated group. CONCLUSIONS: These results suggest that, in rats after renal ablation, heparin may exert its antihypertensive effect, at least in part, by affecting the altered behaviour of resistance vessels during the development phase of hypertension. Increased NO production may contribute to this effect. (+info)
(2/3311) Ambulatory blood pressure monitoring and progression in patients with IgA nephropathy.
BACKGROUND: Hypertension is a recognized marker of poor prognosis in IgA nephropathy. METHODS: The present study investigated the prevalence of white-coat hypertension, the diurnal rhythm of blood pressure (BP), the effectiveness of antihypertensive drug therapy, and the effect of the above on the progression of the kidney disease in IgA nephropathy. One hundred twenty-six IgA nephropathy patients were selected consecutively for 24-h ambulatory blood pressure monitoring (ABPM). Fifty-five patients were normotensive and 71 were treated hypertensives. Their antihypertensive drugs were angiotensin-converting enzyme inhibitors (ACEI) alone or in combination with calcium-channel blockers (CCB). RESULTS: The mean night-time BP of normotensives (108+/-9/67+/-6 mmHg) was significantly lower than their day-time BP (125+/-8/82+/-7 mmHg, P<0.05). There was no significant difference between the mean day-time and night-time BP in hypertensive patients (125+/-9/82+/-7 mmHg vs 128+/-10/85+/-9 mmHg). The circadian variation of BP was preserved ('dippers') in 82% of the normotensive and 7% of the hypertensive patients (P<0.001). There were 10 'white-coat hypertensives' among the patients classified as normotensives with ABPM (mean office blood pressure 149+/-7/96+/-8 mmHg, 24-h blood pressure 127+/-6/83+/-5 mmHg, P<0.05) and 14 among treated hypertensives (mean office BP 152+/-8/98+/-6 mmHg, 24-h BP 130+/-4/85+/-8 mmHg, P<0.05). There was no difference in mean day-time BP among normotensive and treated hypertensive patients (125+/-8/81+/-5 mmHg vs 128+/-10/85+/-9 mmHg). Hypertensives had significantly higher night-time BP (125+/-9/85+/-9 mmHg) than normotensives (108+/-9/67+/-6 mmHg, P<0.001). There was no difference in serum creatinine levels among the different groups at the time of the ABPM. However, thirty-six+/-4.1 months after the ABPM, hypertensive patients (n=52) had higher serum creatinine levels (124+/-32 micromol/l) than at the time of the ABPM (101+/-28 micromol/l). The serum creatinine of normotensive patients (n=43) did not change during the follow-up period. 'Non-dipper' normotensives (n=10) had significantly higher serum creatinine levels at the end of the follow-up period than at its beginning (106+/-17 micromol/l vs 89+/-18 micromol/l, P<0.05). There was no increase in serum creatinine of 'dipper' normotensives. The mean serum creatinine of 'white-coat hypertensives' was significantly higher at the end of the study period than at its beginning. CONCLUSIONS: There is no diurnal blood pressure variation in most of the hypertensive IgA nephropathy patients. ACEI and CCB treatment have better effect on day-time than night-time hypertension. The lack of the circadian rhythm and 'white-coat hypertension' seems to accelerate the progression of IgA nephropathy. (+info)
(3/3311) Effects of calcium-channel blockade in older patients with diabetes and systolic hypertension. Systolic Hypertension in Europe Trial Investigators.
BACKGROUND: Recent reports suggest that calcium-channel blockers may be harmful in patients with diabetes and hypertension. We previously reported that antihypertensive treatment with the calcium-channel blocker nitrendipine reduced the risk of cardiovascular events. In this post hoc analysis, we compared the outcome of treatment with nitrendipine in diabetic and nondiabetic patients. METHODS: After stratification according to center, sex, and presence or absence of previous cardiovascular complications, 4695 patients (age, > or =60 years) with systolic blood pressure of 160 to 219 mm Hg and diastolic pressure below 95 mm Hg were randomly assigned to receive active treatment or placebo. Active treatment consisted of nitrendipine (10 to 40 mg per day) with the possible addition or substitution of enalapril (5 to 20 mg per day) or hydrochlorothiazide (12.5 to 25 mg per day) or both, titrated to reduce the systolic blood pressure by at least 20 mm Hg and to less than 150 mm Hg. In the control group, matching placebo tablets were administered similarly. RESULTS: At randomization, 492 patients (10.5 percent) had diabetes. After a median follow-up of two years, the systolic and diastolic blood pressures in the placebo and active-treatment groups differed by 8.6 and 3.9 mm Hg, respectively, among the diabetic patients. Among the 4203 patients without diabetes, systolic and diastolic pressures differed by 10.3 and 4.5 mm Hg, respectively, in the two groups. After adjustment for possible confounders, active treatment was found to have reduced overall mortality by 55 percent (from 45.1 deaths per 1000 patients to 26.4 deaths per 1000 patients), mortality from cardiovascular disease by 76 percent, all cardiovascular events combined by 69 percent, fatal and nonfatal strokes by 73 percent, and all cardiac events combined by 63 percent in the group of patients with diabetes. Among the nondiabetic patients, active treatment decreased all cardiovascular events combined by 26 percent and fatal and nonfatal strokes by 38 percent. In the group of patients receiving active treatment, reductions in overall mortality, mortality from cardiovascular disease, and all cardiovascular events were significantly larger among the diabetic patients than among the nondiabetic patients (P=0.04, P=0.02, and P=0.01, respectively). CONCLUSIONS: Nitrendipine-based antihypertensive therapy is particularly beneficial in older patients with diabetes and isolated systolic hypertension. Thus, our findings do not support the hypothesis that the use of long-acting calcium-channel blockers may be harmful in diabetic patients. (+info)
(4/3311) Restriction of placental and fetal growth in sheep alters fetal blood pressure responses to angiotensin II and captopril.
1. We have measured arterial blood pressure between 115 and 145 days gestation in normally grown fetal sheep (control group; n = 16) and in fetal sheep in which growth was restricted by experimental restriction of placental growth and development (PR group; n = 13). There was no significant difference in the mean gestational arterial blood pressure between the PR (42.7 +/- 2.6 mmHg) and control groups (37.7 +/- 2.3 mmHg). Mean arterial blood pressure and arterial PO2 were significantly correlated in control animals (r = 0.53, P < 0.05, n = 16), but not in the PR group. 2. There were no changes in mean arterial blood pressure in either the PR or control groups in response to captopril (7.5 microg captopril min-1; PR group n = 7, control group n = 6) between 115 and 125 days gestation. After 135 days gestation, there was a significant decrease (P < 0.05) in the fetal arterial blood pressure in the PR group but not in the control group during the captopril infusion (15 microg captopril min-1; PR group n = 7, control group n = 6). 3. There was a significant effect (F = 14.75; P < 0.001) of increasing doses of angiotensin II on fetal diastolic blood pressure in the PR and control groups. The effects of angiotensin II were different (F = 8.67; P < 0.05) in the PR and control groups at both gestational age ranges. 4. These data indicate that arterial blood pressure may be maintained by different mechanisms in growth restricted fetuses and normally grown counterparts and suggests a role for the fetal renin-angiotensin system in the maintenance of blood pressure in growth restricted fetuses. (+info)
(5/3311) The diameter of the common femoral artery in healthy human: influence of sex, age, and body size.
PURPOSE: To determine the relevance of dilatations of the common femoral artery (CFA), knowledge of the normal CFA diameter is essential. The diameter of the CFA in healthy male and female subjects of different ages was investigated. METHODS: The diameter of the CFA was measured in 122 healthy volunteers (59 male, 63 female; 8 to 81 years of age) with echo-tracking B-mode ultrasound scan. The influence of age, sex, height, weight, body surface area (BSA), and systolic blood pressure was analyzed by means of a multiple regression model. RESULTS: The CFA increased steadily in diameter throughout life. From 25 years onwards, the diameter was larger in men than in women. Significant correlations were found between the CFA diameter and weight (r = 0.58 and r = 0.57 in male and female subjects, respectively; P <.0001), height (r = 0.49 and r = 0.54 in male and female subjects, respectively; P <.0001), and BSA (r = 0.60 and r = 0.62 in male and female subjects, respectively; P <.0001). Age and BSA were used to create a model for prediction of the CFA diameter (r = 0.71 and r = 0.77 in male and female subjects, respectively; P <.0001). CONCLUSION: The diameter of the CFA increases with age, initially during growth but also in adults. This is related to age, body size, and sex male subjects have larger arteries than female subjects. It is now possible to predict the normal CFA diameter, and nomograms that may be used in the study of aneurysmal disease are presented. (+info)
(6/3311) Acute exercise can improve cardioprotection without increasing heat shock protein content.
The aim of this study was to determine the effects of acute bouts of exercise on myocardial recovery after ischemia and heat shock protein expression. Adult female Sprague-Dawley rats were divided into five groups: 1) 1-day run (1DR; n = 6) and 2) 3-day run (3DR; n = 7), in which rats ran for 100 min at a speed of 20 m/min up a 6 degrees grade for 1 or 3 consecutive days; 3) 1-day cold run (1CR), in which rats ran the same as 1DR but with wet fur at 8 degrees C, which prevented an elevation of core temperature (n = 8); 4) heat shock sedentary (HS), in which rats had their core temperatures raised to 42 degrees C one time for 15 min (n = 5); and 5) sedentary control (n=15). Cardiac function was analyzed 24 h after the last treatment using an isolated, working heart model. Nonpaced hearts were initially perfused under normoxic conditions, then underwent 17 min of global, normothermic (37 degrees C) ischemia, and, finally, were allowed to recover for 30 min under normoxic conditions. The concentration of the 72-kDa heat shock protein (HSP 72) was measured in each left ventricle. Compared with that in the sedentary group, recovery of cardiac output x systolic pressure (CO x SP) was enhanced (P < 0.05) in all treatment groups when the postischemic value was covaried with the preischemic value. No differences in CO x SP were found (P > 0.05) between the following groups: 1DR vs. 3DR, 1DR vs. HS, and 1DR vs. 1CR. Heat shock protein concentration was significantly greater (P < 0.05) than that in the sedentary controls in HS, 1DR, and 3DR groups, but not for 1CR. The concentration of HSP 72 was not significantly correlated with postischemic CO x SP (R2 = 0.197, P > 0.05). We conclude that acute bouts of exercise can produce cardioprotective effects without an elevation of HSP 72. (+info)
(7/3311) Echocardiography-derived left ventricular end-systolic regional wall stress and matrix remodeling after experimental myocardial infarction.
OBJECTIVES: We tested the hypothesis that regional end-systolic left ventricular (ESLV) wall stress is associated with extracellular matrix remodeling activity after myocardial infarction (MI). BACKGROUND: Increased left ventricular (LV) wall stress is a stimulus for LV enlargement, and echocardiography can be used to estimate regional wall stress. A powerful validation of a noninvasive method of estimating wall stress would be predicting cellular responses after a MI. METHODS: Echocardiographic images were obtained in rats 1, 7, 14 or 21 days after coronary ligation (n = 11) or sham surgery (n = 5). End-systolic left ventricular wall stress was calculated by finite element analysis in three regions (infarcted, noninfarcted and border) from short-axis images. Matrix metalloproteinase-9 (MMP-9) and macrophage density were determined by immunohistochemistry, and positive cells were counted in high power fields (hpf). RESULTS: Average ESLV wall stress was higher in rats with MI when compared to shams irrespective of time point (p < 0.01), and ESLV wall stress in the infarcted regions increased with time (25.1 +/- 5.9 vs. 69.9 +/- 4.4 kdyn/cm2, day 1 vs. 21; p < 0.01). Matrix metalloproteinase-9 expression was higher in infarcted and border regions when compared to noninfarcted regions (22.1 vs. 25.7 vs. 0.10 cells/hpf, respectively; p < 0.01). Over all regions, ESLV wall stress was associated with MMP-9 (r = 0.76; p < 0.001), macrophage density (r = 0.72; p < 0.001) and collagen content (r = 0.67; p < 0.001). End-systolic left ventricular wall stress was significantly higher when MMP-9 positive cell density was greater than 10 cells/hpf (45+/-20 vs. 14+/-10 kdyn/cm2; p < 0.001). CONCLUSIONS: Regional increases in ESLV wall stress determined by echocardiography-based structural analysis are associated with extracellular matrix degradation activity. (+info)
(8/3311) Chordal force distribution determines systolic mitral leaflet configuration and severity of functional mitral regurgitation.
OBJECTIVES: The purpose of this study was to investigate the impact of the chordae tendineae force distribution on systolic mitral leaflet geometry and mitral valve competence in vitro. BACKGROUND: Functional mitral regurgitation is caused by changes in several elements of the valve apparatus. Interaction among these have to comply with the chordal force distribution defined by the chordal coapting forces (F(c)) created by the transmitral pressure difference, which close the leaflets and the chordal tethering forces (FT) pulling the leaflets apart. METHODS: Porcine mitral valves (n = 5) were mounted in a left ventricular model where leading edge chordal forces measured by dedicated miniature force transducers were controlled by changing left ventricular pressure and papillary muscle position. Chordae geometry and occlusional leaflet area (OLA) needed to cover the leaflet orifice for a given leaflet configuration were determined by two-dimensional echo and reconstructed three-dimensionally. Occlusional leaflet area was used as expression for incomplete leaflet coaptation. Regurgitant fraction (RF) was measured with an electromagnetic flowmeter. RESULTS: Mixed procedure statistics revealed a linear correlation between the sum of the chordal net forces, sigma[Fc - FT]S, and OLA with regression coefficient (minimum - maximum) beta = -115 to -65 [mm2/N]; p < 0.001 and RF (beta = -0.06 to -0.01 [%/N]; p < 0.001). Increasing FT by papillary muscle malalignment restricted leaflet mobility, resulting in a tented leaflet configuration due to an apical and posterior shift of the coaptation line. Anterior leaflet coapting forces increased due to mitral leaflet remodeling, which generated a nonuniform regurgitant orifice area. CONCLUSIONS: Altered chordal force distribution caused functional mitral regurgitation based on tented leaflet configuration as observed clinically. (+info)