Rosuvastatin attenuates hypertension-induced cardiovascular remodeling without affecting blood pressure in DOCA-salt hypertensive rats

The pleiotropic effects of statins represent potential mechanisms for the treatment of end-organ damage in hypertension. This study has investigated the effects of rosuvastatin in a model of cardiovascular remodeling, the DOCA-salt hypertensive rat. Male Wistar rats weighing 300 to 330 g were uninephrectomized (UNX) or UNX and treated with DOCA (25 mg subcutaneously every fourth day) and 1% NaCl in the drinking water. Compared with UNX controls, DOCA-salt rats developed hypertension, cardiovascular hypertrophy, inflammation with perivascular and interstitial cardiac fibrosis, endothelial dysfunction, and prolongation of ventricular action potential duration at 28 days. Rosuvastatin-treated rats received 20mg/kg/d of the drug in 10% Tween 20 by oral gavage for 32 days commencing 4 days before uninephrectomy. UNX and DOCA-salt controls received vehicle only. Rosuvastatin therapy attenuated the development of cardiovascular hypertrophy, inflammation, fibrosis, and ventricular action potential prolongation, but did not modify hypertension or vascular dysfunction. We conclude that the pleiotropic effects of rosuvastatin include attenuation of aspects of cardiovascular remodeling in the DOCA-salt model of hypertension in rats without altering systolic blood pressure.

The prevalence and impact of overweight and obesity in an Australian obstetric population

Objective: To assess the prevalence and impact of overweight and obesity in an Australian obstetric population. Design, setting and participants: The Mater Mother's Hospital (MMH), South Brisbane, is an urban tertiary referral maternity hospital. We reviewed data for the 18401 women who were booked for antenatal care at the MMH, delivered between January 1998 and December 2002, and had a singleton pregnancy. Of those women, 14 230 had an estimated pre-pregnancy body mass index (BMI) noted in their record; 2978 women with BMI 40 kg/m(2)). Main outcome measures: Prevalence of overweight and obesity in an obstetric population; maternal, peripartum and neonatal outcomes associated with raised BMI. Results: Of the 14230 women, 6443 (45%) were of normal weight, and 4809 (34%) were overweight, obese or morbidly obese. Overweight, obese and morbidly obese women were at increased risk of adverse outcomes (figures represent adjusted odds ratio [AOR] [95% Cl]): hypertensive disorders of pregnancy (overweight 1.74 [1.45-2.15], obese 3.00 [2.40-3.74], morbidly obese 4.87 [3.27-7.24]); gestational diabetes (overweight 1.78 [1.25-2.52], obese 2.95 [2.05-4.25], morbidly obese 7.44 [4.42-12.54]); hospital admission longer than 5 days (overweight 1.36 [1.13-1.63], obese 1.49 [1.21-1.86], morbidly obese 3.18 [2.19-4.61]); and caesarean section (overweight 1.50 [1.36-1.66], obese 2.02 [1.79-2.29], morbidly obese 2.54 [1.94-3.321). Neonates born to obese and morbidly obese women had an increased risk of birth defects (obese 1.58 (1.02-2.46], morbidly obese 3.41 [1.67-6.94]); and hypoglycaemia (obese 2.57 [1.39-4.78], morbidly obese 7.14 [3.04-16.74]). Neonates born to morbidly obese women were at increased risk of admission to intensive care (2.77 [1.81-4.25]); premature delivery (< 34 weeks' gestation) (2.13 [1.13-4.01]); and jaundice (1.44 [1.09-1.89]). Conclusions: Overweight and obesity are common in pregnant women. Increasing BMI is associated with maternal and neonatal outcomes that may increase the costs of obstetric care. To assist in planning health service delivery, we believe that BMI should be routinely recorded on perinatal data collection sheets

Perindopril, an angiotensin converting enzyme inhibitor, in pulmonary hypertensive rats: comparative effects on pulmonary vascular structure and function

1 Hypoxic pulmonary hypertension in rats (10% O-2, 4 weeks) is characterized by changes in pulmonary vascular structure and function. The effects of the angiotensin converting enzyme inhibitor perindopril (oral gavage, once daily for the 4 weeks of hypoxia) on these changes were examined. 2 Perindopril (30 mg kg(-1) d(-1)) caused an 18% reduction in pulmonary artery pressure in hypoxic rats. 3 Structural changes (remodelling) in hypoxic rats included increases in (i) critical closing pressure in isolated perfused lungs (remodelling of arteries (50 mu m 0.d.) and (ii) medial wall thickness of intralobar pulmonary arteries, assessed histologically (vessels 30-100 and 101-500 mu m o.d.). Perindopril 10 and 30 mg kg(-1) d(-1) attenuated remodelling in vessels less than or equal to 100 mu m (lungs and histology), 30 mg kg(-1) d(-1) was effective in vessels 101-500 mu m but neither dose prevented hypertrophy of main pulmonary artery. 3 mg kg(-1) d(-1) was without effect. 4 Perindopril (30 mg kg(-1) d(-1)) prevented the exaggerated hypoxic pulmonary vasoconstrictor response seen in perfused lungs from hypoxic rats but did not prevent any of the functional changes (i.e. the increased contractions to 5-HT, U46619 (thromboxane-mimetic) and K+ and diminished contractions to angiotensins I and II) seen in isolated intralobar or main pulmonary arteries. Acetylcholine responses were unaltered in hypoxic rats. 5 We conclude that, in hypoxic rats, altered pulmonary vascular function is largely independent of remodelling. Hence any drug that affects only remodelling is unlikely to restore pulmonary vascular function to normal and, like perindopril, may have only a modest effect on pulmonary artery pressure.

L-arginine improves cardiovascular function in DOCA-salt hypertensive rats

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