Apoptosis or programmed cell death frequently parallels abnormalities in cell proliferation and differentiation. As hypertrophy/hyperplasia or remodeling occurs in organs affected by hypertension, we evaluated the degree of apoptosis in the heart, kidney, and brain in situ in genetically hypertensive mice and rats as well as in cultured vascular smooth muscle cells. Apoptosis was characterized by morphological features, DNA fragmentation, and laddering as well as by terminal deoxynucleotidyl transferase labeling of the 3' OH ends of both extracted DNA and tissue sections. The present report provides the first evidence of increased apoptosis in whole organs of genetically hypertensive rat and mouse strains: in the heart of spontaneously hypertensive rats (SHR) and in the heart (ventricular cardiomyocytes), kidney (inner cortex and medulla), and brain (cortex, striatum, hippocampus, and thalamus) of spontaneously hypertensive mice, with a higher effect of apoptotic inducers in cultured aortic smooth muscle cells derived from SHR. Both types of known apoptotic processes, oligonucleosomal cleavage and large DNA fragmentation, were observed in vascular smooth muscle cells, but only the former appeared to be increased in SHR. This study underlines the importance of cell death dysregulation in hypertension, reveals a new route for investigation of the pathogenesis of hypertension, and suggests novel targets of therapeutic intervention.

Abstract-The purpose of the present study was to evaluate the relationship of aldosterone to blood pressure and left ventricular size in black American (nϭ109) and white French Canadian (nϭ73) patients with essential hypertension. Measurements were obtained with patients off antihypertensive medications and included 24-hour blood pressure monitoring, plasma renin activity and aldosterone, and an echocardiogram. Compared with the French Canadians, the black Americans had higher body mass indexes, higher systolic blood pressures, attenuated nighttime reduction of blood pressure, and lower serum potassium concentrations (PϽ0.01 for each). Left ventricular mass index, posterior wall thickness, interventricular septal thickness, and relative wall thickness were also greater (PϽ0.01 for each) in the black American patients. Supine and standing plasma renin activity was lower (PϽ0.01 and PϽ0.05, respectively) in the black Americans, whereas supine plasma aldosterone concentrations did not differ, and standing plasma aldosterone was greater (PϽ0.05) in the black Americans (9.2Ϯ0.7 ng/dL) than in the French Canadians (7.3Ϯ0.6 ng/dL). In the black Americans, supine plasma aldosterone was positively correlated with nighttime systolic (rϭ0. Key Words: race Ⅲ aldosterone Ⅲ echocardiography Ⅲ left ventricle Ⅲ obesity Ⅲ plasma renin activity A ldosterone is a potent mineralocorticoid that promotes sodium retention and elevation of arterial pressure. Independent of its effect on blood pressure, aldosterone may also play a role in cardiac hypertrophy. Within the myocardium, aldosterone acts via mineralocorticoid receptors to enhance extracellular matrix and collagen deposition. 1 In animal models, both cardiac load and high circulating aldosterone levels stimulate fibrosis within the myocardium, leading to left ventricular hypertrophy (LVH). 2 Pathological patterns of LV geometry have also been associated with elevations of plasma aldosterone concentrations in patients with essential hypertension, 3,4 and the early onset of LVH has been described in patients with primary aldosteronism. 5 The prevalence of hypertension in US blacks is 50% greater than that in whites in either the United States or Canada. 6,7 Plasma renin activity (PRA) tends to be suppressed in hypertensive blacks, 8 and blacks have a high prevalence of salt-sensitive hypertension. 9 In addition, among hypertensives, blacks have a higher prevalence of LVH and a 6-fold higher prevalence of concentric LV remodeling than do whites. 10 -14 The purpose of the present study was to evaluate the relationship of aldosterone to both blood pressure and LV geometry in both black and white patients with essential hypertension. MethodsIn conjunction with ongoing collaborative studies of the genetic determinants of hypertension, black American patients were studied

Since a negative calcium balance is present in spontaneously hypertensive rats, we searched for the gene(s) involved in this dysregulation. A cDNA library was constructed from the spontaneously hypertensive rat parathyroid gland, which is a key regulator of serum-ionized calcium. From seven overlapping DNA fragments, a 1100-base pair novel cDNA containing an open reading frame of 224 codons was reconstituted. This novel gene, named HCaRG (hypertension-related, calcium-regulated gene), was negatively regulated by extracellular calcium concentration, and its basal mRNA levels were higher in hypertensive animals. The deduced protein showed no transmembrane domain, 67% ␣-helix content, a mutated calcium-binding site (EF-hand motif), four putative "leucine zipper" motifs, and a nuclear receptor-binding domain. At the subcellular level, HCaRG had a nuclear localization. We cloned the human homolog of this gene. Sequence comparison revealed 80% homology between rats and humans at the nucleotide and amino acid sequences. Tissue distribution showed a preponderance in the heart, stomach, jejunum, kidney (tubular fraction), liver, and adrenal gland (mainly in the medulla). HCaRG mRNA was significantly more expressed in adult than in fetal organs, and its levels were decreased in tumors and cancerous cell lines. We observed that after 60-min ischemia followed by reperfusion, HCaRG mRNA declined rapidly in contrast with an increase in c-myc mRNA. Its levels then rose steadily to exceed base line at 48 h of reperfusion. HEK293 cells stably transfected with HCaRG exhibited much lower proliferation, as shown by cell count and [ 3 H]thymidine incorporation. Taken together, our results suggest that HCaRG is a nuclear protein potentially involved in the control of cell proliferation.Ionized calcium concentration in plasma is maintained within a very narrow range. The major players maintaining extracellular calcium homeostasis are calciotropic hormones, parathyroid hormone (PTH), 1 1,25-dihydroxyvitamin D, calcitonin, and calcium itself. Indeed, extracellular calcium regulates its own concentration as an extracellular messenger by acting on calcium receptors or calcium sensors. The calciumsensing receptor is linked to several intracellular second messenger systems via guanylyl nucleotide-regulating G proteins and activates phosphoinositide-specific phospholipase C, leading to accumulation of inositol 1,4,5-trisphosphate and diacylglycerol (1-5).