Eplerenone prevents salt-induced vascular remodeling and cardiac fibrosis in stroke-prone spontaneously hypertensive rats

We examined the effect of different levels of salt intake on the role of aldosterone on cardiac and vascular changes in salt-loaded stroke-prone spontaneously hypertensive rats (SHRSP). Eleven-week-old SHRSP were fed high-salt (4.2% NaCl), normal-salt (0.28%), or low-salt (0.03%) diets with or without eplerenone (100 mg/kg per day, in food) for 5 weeks. A group of high-salt SHRSP was also treated with hydralazine (25 mg/kg per day). Blood pressure increased more in high-salt rats than in other groups (P<0.001). Eplerenone prevented further blood pressure rise in salt-loaded rats, with little effect on control and low-salt SHRSP. Increased media-to-lumen ratio of mesenteric resistance arteries induced by salt (P<0.01) was prevented by eplerenone (P<0.01). Maximal acetylcholine-induced vasodilation was impaired under salt loading (P<0.01), but improved under eplerenone (P<0.01). Eplerenone prevented (P<0.01) increased heart weight and left and right ventricular collagen deposition induced by high salt. Blood pressure lowering by hydralazine in high-salt SHRSP did not influence endothelial function or left ventricular collagen. Our study demonstrates salt-dependency of aldosterone effects on severity of hypertension, endothelial dysfunction, and cardiac and vascular remodeling in SHRSP. These effects were attenuated by eplerenone, particularly in the salt-loaded state, underlining the pathophysiological role of aldosterone in salt-sensitive hypertension

Reduced vascular remodeling, endothelial dysfunction, and oxidative stress in resistance arteries of Angiotensin II-infused macrophage colony-stimulating factor-deficient mice: evidence for a role in inflammation in Angiotensin-induced vascular injury

<b>Objective—</b> Angiotensin (Ang) II-induced vascular damage may be partially mediated by reactive oxygen species generation and inflammation. Homozygous osteopetrotic mice (Op/Op), deficient in macrophage colony-stimulating factor (m-CSF), exhibit reduced inflammation. We therefore investigated Ang II effects on vascular structure, function, and oxidant stress generation in this model.<p></p> <b>Methods and Results—</b> Adult Op/Op, heterozygous (Op/+), and wild type (+/+) mice underwent 14-day Ang II (1000 ng/kg per minute) or saline infusion. Blood pressure (BP) was assessed by radiotelemetry, mesenteric resistance artery vascular reactivity was studied on a pressurized myograph, and vascular superoxide and NAD(P)H oxidase activity by lucigenin chemiluminescence. Ang II increased BP in Op/+ and +/+ mice but not in Op/Op. Ang II-treated Op/+ and +/+ mice showed reduced acetylcholine-mediated relaxation (maximal relaxation, respectively, 64% and 67% versus 84% and 93% in respective controls; P<0.05), which was unaffected by l-NAME. Ang II-infused Op/Op mice arteries showed significantly less endothelial dysfunction than vehicle-infused counterparts (maximal relaxation 87% versus 96% in shams). Resistance arteries from Ang II-infused +/+ and Op/+ mice had significantly increased media-to-lumen ratio and media thickness, neither of which was altered in Op/Op mice compared with untreated littermates. Vascular media cross-sectional area, NAD(P)H oxidase activity and expression, and vascular cell adhesion molecule (VCAM)-1 expression were significantly increased by Ang II only in +/+ mice (P<0.05).<p></p> <b>Conclusions—</b> m-CSF–deficient mice (Op/Op) developed less endothelial dysfunction, vascular remodeling, and oxidative stress induced by Ang II than +/+ littermates, suggesting a critical role of m-CSF and proinflammatory mediators in Ang II-induced vascular injury

Severe Hypertension and Massive Osteoporosis as Presenting Symptoms of Cushing’s Syndrome

Though Cushing's syndrome is a well-known clinical problem in terms of side effects of steroid therapy, endogenous Cushing's syndrome is a relatively rare diagnosis. We treated a 27-year-old patient who presented with severe hypertension and massive osteoporosis. We could diagnose a central Cushing syndrome by endocrinological function tests which, in retrospect, existed undiagnosed for more than 5 years. However, magnetic resonance imaging did not display an adenoma neither of the hypophysis nor of the adrenal glands. During explorative surgery, a cylindric microadenoma of the pituitary gland was found and excised. After surgery, the blood pressure returned to normal, making further antihypertensive treatment unnecessary. Copyright (C) 2001 S. Karger AG, Basel

Persistent remodeling of resistance arteries in type 2 diabetic patients on antihypertensive treatment

We hypothesized that resistance arteries from diabetic patients with controlled hypertension have less remodeling than vessels from untreated hypertensive subjects. Eight normotensive subjects (aged 44±3 years, 3 men; values are mean±SEM), 19 untreated hypertensive subjects (46±2 years, 9 men), and 23 hypertensive subjects with type 2 diabetes mellitus under antihypertensive treatment (58±1 years, 15 men) were studied. Resistance arteries dissected from gluteal subcutaneous tissue were assessed on a pressurized myograph. Most diabetic patients (70%) were being treated with angiotensin-converting enzyme inhibitors. Although systolic blood pressure was still above the normotensive range in these patients (144±2 versus 150±3 mm Hg in hypertensive and 114±4 mm Hg in normotensive subjects), diastolic blood pressure was well controlled (83±2 mm Hg) and significantly lower compared with that in untreated hypertensives (100±1 mm Hg; P<0.001) but higher than in normotensives (76±3 mm Hg; P<0.05). Thus, pulse pressure was higher in diabetic patients (P<0.05). The media-to-lumen ratio of resistance arteries was greater in hypertensives (0.083±0.002) compared with normotensive controls (0.059±0.003; P<0.05) and was even higher in diabetic hypertensive subjects (0.105±0.004; P<0.001 versus normotensive controls). The medial cross-sectional area was greater in diabetic and hypertensive patients compared with normotensive controls (P<0.001). Acetylcholine-induced relaxation was impaired in vessels from hypertensive patients and from patients with both diabetes mellitus and hypertension (P<0.05 versus normotensive controls), whereas endothelium-independent vasorelaxation was similar in all groups. Despite effective antihypertensive treatment, resistance arteries from hypertensive diabetic patients showed marked remodeling, greater than that of vessels from untreated, nondiabetic, hypertensive subjects, in agreement with the high cardiovascular risk of subjects suffering from both diabetes and hypertension

The Macrocirculation and Microcirculation of Hypertension.

Changes in vascular structure that accompany hypertension may contribute to hypertensive end-organ damage. Both the macrovascular and microvascular levels should be considered, as interactions between them are believed to be critically important. Regarding the macrocirculation, the article first reviews basic concepts of vascular biomechanics, such as arterial compliance, arterial distensibility, and stress-strain relationships of arterial wall material, and then reviews how hypertension affects the properties of conduit arteries, particularly examining evidence that it accelerates the progressive stiffening that normally occurs with advancing age. High arterial stiffness may increase central systolic and pulse pressure by two different mechanisms: 1) Abnormally high pulse wave velocity may cause pressure waves reflected in the periphery to reach the central aorta in systole, thus augmenting systolic pressure; 2) In the elderly, the interaction of the forward pressure wave with high arterial stiffness is mostly responsible for abnormally high pulse pressure. At the microvascular level, hypertensive disease is characterized by inward eutrophic or hypertrophic arteriolar remodeling and capillary rarefaction. These abnormalities may depend in part on the abnormal transmission of highly pulsatile blood pressure into microvascular networks, especially in highly perfused organs with low vascular resistance, such as the kidney, heart, and brain, where it contributes to hypertensive end-organ damage