For decades, essential hypertension has been primarily viewed from a hemodynamic, neural, and renal perspective. However, based on mounting evidence from clinical, epidemiological, and experimental studies, it has become increasingly recognized that disturbances in carbohydrate and lipid metabolism often accompany high blood pressure, and that essential hypertension may also represent a disorder of cardiovascular endocrinology and metabolism (1, 2). In patients with essential hypertension, clustering of metabolic cardiovascular risk factors -including glucose intolerance, hyperinsulinemia, and hypertriglyceridemiamay promote susceptibility to target organ damage and partly explain why conventional antihypertensive agents have failed to reduce the risk for coronary heart disease to the extent predicted from epidemiological studies (2).Recently, a provocative hypothesis has emerged in which inherited disorders of carbohydrate or lipid metabolism are held to be at the core of the hypertension syndrome and to contribute to the primary pathogenesis of increased blood pressure. Studies in nonobese subjects with a family history of hypertension and in a variety of experimental animal models have suggested that alterations in carbohydrate and/or lipid metabolism can influence the regulation of blood pressure and might precede the development of hypertension (3-5). The lack of insulin resistance in patients with secondary forms of hypertension, together with observations of disordered carbohydrate and lipid metabolism in cultured adipocytes from hypertensive animals, indicates that at least some endocrine-metabolic disturbances are not simply a consequence of increased blood pressure (4,(6)(7)(8). Hence, there is intense interest in identifying genetic mechanisms that may underlie the association between increased blood pressure and other cardiovascular risk factors in essential hypertension.The spontaneously hypertensive rat (SHR) is the most Disorders of carbohydrate and lipid metabolism have been reported to cluster in patients with essential hypertension and in spontaneously hypertensive rats (SHRs). A deletion in the Cd36 gene on chromosome 4 has recently been implicated in defective carbohydrate and lipid metabolism in isolated adipocytes from SHRs. However, the role of Cd36 and chromosome 4 in the control of blood pressure and systemic cardiovascular risk factors in SHRs is unknown. In the SHR.BN-Il6/Npy congenic strain, we have found that transfer of a segment of chromosome 4 (including Cd36) from the Brown Norway (BN) rat onto the SHR background induces reductions in blood pressure and ameliorates dietary-induced glucose intolerance, hyperinsulinemia, and hypertriglyceridemia. These results demonstrate that a single chromosome region can influence a broad spectrum of cardiovascular risk factors involved in the hypertension metabolic syndrome. However, analysis of Cd36 genotypes in the SHR and stroke-prone SHR strains indicates that the deletion variant of Cd36 was not critical to the initial selection for hypert...

No abstract

Abnormalities in carbohydrate and lipid metabolism are common in patients with essential hypertension and in the spontaneously hypertensive rat (SHR). To identify chromosome regions contributing to this clustering of cardiovascular risk factors in the SHR, we searched for quantitative trait loci (QTL) associated with insulin resistance, glucose intolerance, and dyslipidemia by using the HXB/BXH recombinant inbred (RI) strains. Analysis of variance in RI strains suggested significant effects of genetic factors. A genome screening of the RI strains with more than 700 markers revealed QTL significantly associated with insulin resistance on Chromosomes (Chrs) 3 and 19. The Chr 19 QTL was confirmed by testing a previously derived SHR-19 congenic strain: transfer of a Chr 19 segment delineated by markers D19Rat57 and D19Mit7 from the Brown Norway (BN/Cr) strain onto the genetic background of the SHR/Ola was associated with decreased insulin and glucose concentrations and ameliorated insulin resistance at the tissue level. These findings suggest that closely linked genes on Chr 19, or perhaps even a single gene with pleiotropic effects, influence the clustering of metabolic disturbances in the SHR-BN model.

No abstract

The aim of the study was to examine whether the circulating cell adhesion molecules, von Willebrand factor (vWf) and endothelin-1, are elevated in patients with essential hypertension with no other risk factors for atherosclerosis and thus may serve as a markers of endothelial dysfunction in uncomplicated hypertension. Furthermore, the effect of treatment with the ACE inhibitor, quinapril, on levels of endothelial dysfunction markers were studied. The levels of adhesion molecules (intercellular cell adhesion molecule-1 [ICAM-1], E-selectin, P-selectin), von Wilebrand factor (vWf) and endothelin-1 were measured in patients with hypertension without any other risk factors of atherosclerosis before and after treatment with quinapril (n = 22) and in normotensive controls (n = 22). Compared with normotensive subjects, the hypertensive patients had significantly higher levels of ICAM-1 (238 vs 208 ng/ml, P = 0.02), vWf (119 vs 105 IU/dl, P Ͻ 0.05) and endothelin-1 (5.76 vs 5.14 fmol/ml, P Ͻ 0.05). Three-month treatment of hyper-