Effect of bariatric surgery on cardiac structure and function in obese patients: Role of the renin‐angiotensin system

Echocardiographic alterations have been described in obesity, but their modifications after bariatric surgery (BS) and mechanisms are little known, mostly in normotensive patients. We aimed to analyze cardiac changes 1 year post‐BS and to explore possible mechanisms. A cohort of patients with severe obesity (58% normotensives) were prospectively recruited and examined before surgery and after 12 months. Clinical and echocardiographic data, 24 h BP, renin‐angiotensin‐aldosterone system (RAAS) components, cytokines, and inflammatory markers were analyzed at these two time points. Overall reduction in body weight was mean (IQR) = 30.0% (25.9–33.8). There were statistically significant decreases in left ventricle mass index^2.7(LVMI)^2.7, septum thickness (ST), posterior wall thickness (PWT), relative wall thickness (RWT), and E/e’, both in the whole cohort and in patients without RAAS blockers (p ≤ .04 for all). Plasma renin activity (PRA) decreased from (median, IQR) = 0.8 (0.3;1.35) to 0.4 (0.2;0.93) ng/ml/h, plasma aldosterone from 92 (58.6;126) to 68.1 (56.2;83.4) ng/dl, and angiotensin‐converting enzyme (ACE)‐2 activity from 7.7 (5.7;11.8) to 6.8 (5.3;11.2) RFU/µl/h, p < .05. The body weight loss correlated with a decrease in both 24 h SBP and 24 h DBP (Pearson''s coefficient 0.353, p = .022 and 0.384, p = .012, respectively). Variation (Δ) of body weight correlated with ΔE/e’ (Pearson''s coeff. 0.414, p = .008) and with Δ lateral e’ (Pearson''s coeff. = −0.363, p = .018). Generalized linear models showed that ΔPRA was an independent variable for the final (12‐months post‐BS) LVMI^2.7 (p = .028). No other changes in cardiac parameters correlated with ΔBP. In addition to the respective baseline value, final values of PWT and RWT were dependent on 12‐month Δ of PRA, ACE, and ACE/ACE2 (p < .03 for all). We conclude that there are cardiac changes post‐BS in patients with severe obesity, normotensives included. Structural changes appear to be related to modifications in the renin‐angiotensin axis.     

阻断肾内肾素-血管紧张素系统对转化生长因子β1mRNA及细胞外基质表达的作用

目的探讨苯那普利延缓肾脏疾病进展的可能作用机制。方法采用实验性肾小球硬化模型,治疗组给苯那普利（４ｍｇ·ｋｇ－１·ｄ－１）。用比色法和放免法分别测定肾内血管紧张素转换酶（ＡＣＥ）活性和血管紧张素Ⅱ（ＡｎｇⅡ）含量,免疫组化检测肾组织转化生长因子β１（ＴＧＦβ１）和细胞外基质（ＥＣＭ）,原位杂交观察ＴＧＦβ１ｍＲＮＡ表达。结果治疗组肾内ＡＣＥ活性和ＡｎｇⅡ与非治疗组比较,受到明显抑制（Ｐ＜０．０１）。治疗组肾小球和肾小管区ＴＧＦβ１ｍＲＮＡ表达量显著低于非治疗组（Ｐ＜００１）。同时,ＥＣＭ在肾小球内沉积也较非治疗组显著减少（Ｐ＜０．０１）。结论苯那普利通过阻断肾内肾素血管紧张素系统,在下调ＴＧＦβ１表达和ＥＣＭ积聚中起重要作用。     

Effect of Antihypertensive Therapy on Aortic Distensibility in Patients with Essential Hypertension: Comparison with Trichlormethiazide, Nicardipine and Alacepril

To assess the effect of antihypertensive drugs on aortic distensibility, we evaluated the aortic distensibility of 33 hypertensive patients before and after antihypertensive treatment by using cine magnetic resonance imaging. Thirty three hypertensive patients were divided into three groups and treated for 12 weeks with 2–4 mg trichlormethiazide per day (n = 10), 80 mg nicardipine per day (n = 13) and 50 mg alacepril per day (n = 10). There were no significant differences in mean age and mean blood pressure among the three groups. Cine magnetic resonance was performed at ascending and descending aortic levels. Aortic area was measured at the maximum and minimum frames. The effect of antihypertensive therapy on aortic distensibility was evaluated as the percent change from before treatment to after treatment. There were no significant differences in pulse pressure before and after treatment with trichlormethiazide, nicardipine and alacepril. After treatment with these drugs, mean blood pressure in all groups decreased (trichlormethiazide and nicardipine, P < .01; alacepril, P < .05), (the maximum area - the minimum area) and aortic distensibility in all groups increased significantly (each P < .01). Percent changes in aortic distensibility after treatment were significantly higher with nicardipine (ascending, 346.6 ± 255.9%; descending, 338.8 ± 246.5%, each P < .05) and alacepril (ascending, 369.7 ± 238.8%, P < .05; descending, 306.9 ± 123.3%, P < .01) than with trichlormethiazide (ascending, 146.0 ± 139.6%; descending, 129.3 ± 97.5%). In conclusion, nicardipine and alacepril have a beneficial effect on aortic distensibility.     

Bisoprolol and Captopril Effects on Insulin Receptor Tyrosine Kinase Activity in Essential Hypertension

Angiotension converting enzyme (ACE) inhibitors and β-blockers have been reported to possess disparate effects on insulin sensitivity. The aim of this study was to study the effects of the selective β-1 blocker bisoprolol and of the ACE inhibitor captopril on cellular insulin action in hypertensive individuals. After washout, 12 mild to moderate essential hypertensives were randomized in a double-blind manner to 5 mg bisoprolol daily or 25 mg captopril twice daily for 8 weeks. Erythrocyte insulin binding and insulin-stimulated tyrosine kinase (TK) activity were measured before and after therapy. Both agents decreased diastolic blood pressure significantly (bisoprolol 96.5 ± 0.9 to 87.8 ± 3.1 mm Hg; captopril 96.5 ± 0.9 to 91.5 ± 1.8 mm Hg; P < .05). Fasting plasma glucose, insulin, and insulin/glucose indices remained unchanged after both therapies, as did lipid profiles. Maximal insulin-stimulated TK activity, assessed by phosphorylation of the exogenous substrate poly-Glu₈₀Tyr₂₀, was significantly higher (P < .05) after bisoprolol treatment, but not after captopril treatment, when compared to placebo (bisoprolol 8.5 ± 1.8; captopril 7.3 ± 1.5; placebo: 6.4 ± 1.3 pmol ³²P-ATP/fmol bound insulin). However, captopril, but not bisoprolol, increased the sensitivity of the receptor TK activity, as measured by the half-maximal activity concentration (ED₅₀). Specific insulin binding was not affected by these two agents. Thus, both captopril and bisoprolol may have favorable but different effects on TK activity and insulin action at the cellular level.     

Effects of an ACE Inhibitor and a Calcium Channel Blocker on Cardiovascular Autonomic Nervous System and Carotid Distensibility in Patients with Mild to Moderate Hypertension

We investigated the relationship between cardiovascular autonomic nervous system function and carotid arterial distensibility during treatment with an angiotensin converting enzyme inhibitor (derapril) or a calcium channel blocker (manidipine) for hypertension. In 37 patients with hypertension, autonomic function was assessed by heart rate variability and baroreceptor sensitivity using phenylephrine injection. Left ventricular mass index and carotid arterial distensibility were assessed by ultrasound examinations. Before the medication, both baroreceptor sensitivity and heart rate variability correlated with carotid arterial distensibility, but not with left ventricular mass index by multiple regression analysis. Subsequently, patients were randomly allocated into two groups, derapril (n = 18) and manidipine (n = 19) for 20 weeks. At the end of the study, the change in baroreceptor sensitivity correlated with change in carotid arterial distensibility (r = 0.41, P < .05), but not with change in left ventricular mass index. Although derapril and manidipine decreased blood pressure and left ventricular mass index to the same extent, the former improved heart rate variability, baroreceptor sensitivity (5.0 ± 1.9 → 5.6 ± 2.0 msec/mm Hg), and carotid arterial distensibility (2.1 ± 0.8 → 2.5 ± 1.0 %kPa), but the latter did not improve them at all. Thus, impairment of the autonomic balance was related to the impairment of carotid arterial distensibility in hypertension; derapril, but not manidipine, significantly improved these abnormalities.     

Effects of cyclooxygenase inhibition on endothelial function in hypertensive patients treated with angiotensin-converting enzyme inhibitors

BACKGROUND: Cyclooxygenase inhibition restores endothelium-dependent vasodilatation in hypertension, but it is unknown whether it restores endothelial function in hypertensive patients treated with angiotensin-converting enzyme (ACE) inhibitors. HYPOTHESIS: The purpose of the present study was to evaluate the effects of cyclooxygenase inhibition on endothelial function in hypertensive patients treated with ACE inhibitors. METHODS: Endothelium-dependent flow-mediated dilatation (FMD) and endothelium-independent glyceryl trinitrate-induced dilatation were investigated in 10 patients treated with enalapril (ACE group), 11 patients treated with manidipine and metoprolol (non-ACE group), and 12 normotensive control subjects. After administration of 1000 mg of aspirin, FMD was investigated once again. Plasma cyclic guanosine monophosphate (cGMP) and eicosanoids were also measured during reactive hyperemia before and after aspirin administration. RESULTS: Flow-mediated dilatation was more impaired in the non-ACE group than in the ACE group (8.3 +/- 3.8%, 5.7 +/- 1.7%, respectively, p<0.04). Glyceryl trinitrate-induced dilatation was similar in the ACE group, the non-ACE group, and in the control subjects. In the ACE group, FMD was reduced after administration of aspirin (5.3 +/- 4.2%, p<0.05). The percent change in FMD after administration of aspirin correlated significantly with percent change in cGMP (r=0.77, p<0.03; y-intercept, -62.1%, p<0.01). After aspirin administration, levels of thromboxane B2 and 6-keto-prostaglandin(1alpha) were significantly decreased compared with those before aspirin administration in all groups. CONCLUSIONS: Cyclooxygenase inhibition may reduce the beneficial effect on endothelium-dependent vasodilatation induced by ACE inhibitors. The results suggested that prostacyclin in addition to nitric oxide plays a significant role in the restoration of endothelial function in hypertensive patients treated with ACE inhibitors.     

ARB与ACEI联合用药治疗老年糖尿病肾病的临床观察

目的观察ARB与ACEI联合应用和单用ACEI或ARB治疗老年糖尿病患者的疗效比较。方法67例临床确诊的2-DM肾病患者随机分成3组，A组用ACEI治疗27例，B组用ARB治疗12例。C组用ARB联合ACEI治疗28例。观察2个月后血压，血BUN、Cr、24h尿蛋白定量、电解质的变化。结果3组的血压及24h尿蛋白均明显下降，尤其是C组，以上作用更为显著。结论对老年糖尿病肾病患者而言，联合应用ACEI和ARB具有更好的肾脏保护作用。对延缓DM的发展，可能具有重要价值。