High dietary sodium has been adduced as a cause of hypertension and its target organ damage for millennia; yet careful observations using sophisticated techniques have revealed only a weak relationship between sodium intake/excretion and blood pressure in the general population. Further, studies of the effects of dietary sodium reduction on blood pressure have revealed minimal achieved reductions in blood pressure, no relationship between the magnitude of reduction in sodium intake/excretion and the blood pressure effect, and no evidence of an effect of sodium reduction on death or cardiovascular events. While blood pressure in the population as a whole is only modestly responsive to alterations in sodium intake, some individuals manifest large blood pressure changes in response to acute or chronic salt depletion or repletion, and are termed "salt sensitive". Salt sensitivity and resistance have a large variety of determinants, including genetic factors, race/ethnicity, age, body mass and diet (overall diet quality, macro- and micronutrient content), as well as associated disease states, e.g. hypertension, diabetes and renal dysfunction. Salt sensitivity can be modulated by improving the quality of the diet, e.g. the DASH diet reduced salt sensitivity by increasing the slope of the pressure-natriuresis curve. Mechanisms that appear to contribute to salt sensitivity include blunted activity of the renin-angiotensin-aldosterone system, deficiency in atrial natriuretic peptide expression, and blunted arterial baroreflex sensitivity. Salt sensitivity in both normotensive and hypertensive persons has been associated with increased cardiovascular disease events and reduced survival. Increased attention to strategies that reduce salt sensitivity, i.e. improvement in diet quality and weight loss, particularly in high risk persons, is urgently needed.

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Anopheles coustani s.l. and Anopheles squamosus are sub-Saharan mosquito species that have been implicated in malaria transmission. Although generally believed to be of negligible importance due to their overwhelmingly zoophilic behavior, An. coustani s.l. and An. squamosus made up a large proportion of the anophelines collected by human landing catches during the

Abstract-We hypothesized that a single copy of the proatrial natriuretic peptide gene (Nppa ϩ/Ϫ ) would not be adequate to protect heterozygous mice against exaggerated cardiac hypertrophy and remodeling after pressure-overload stress. Nppa ϩ/ϩ , Nppa ϩ/Ϫ , and Nppa Ϫ/Ϫ mice were subjected to sham surgery or transverse aortic constriction and fed a basal salt diet. Heart weight varied inversely with Nppa gene load by 1 week after either surgery. Fractional shortening did not differ among genotypes at baseline and fell in Nppa Ϫ/Ϫ mice only after transverse aortic constriction. There was a graded response in collagen deposition related to atrial natriuretic peptide (ANP) expression after either surgery. A robust interstitial and perivascular fibrosis was noted in Nppa Ϫ/Ϫ and Nppa ϩ/Ϫ but not in Nppa ϩ/ϩ mice after transverse aortic constriction. Our findings are consistent with a growing body of evidence that ANP is an important modulator of cardiac hypertrophy and remodeling in response to hemodynamic stress. The observation that partial ANP deficiency results in exaggerated hypertrophy and remodeling after pressure overload suggests that genetic or environmental variation in ANP levels may play a role in the development of cardiac hypertrophy, remodeling, and failure in humans. Key Words: atrial natriuretic factor Ⅲ natriuretic peptides Ⅲ receptors, atrial natriuretic factor Ⅲ hypertrophy, cardiac Ⅲ remodeling Ⅲ extracellular matrix Ⅲ collagen R ecent studies suggest that atrial natriuretic factor (ANP) is an autocrine/paracrine modulator of cardiac hypertrophy and remodeling in response to pathologic stimuli. [1][2][3][4][5][6][7][8][9][10] Mice with homozygous deletion of the pro-ANP gene (Nppa Ϫ/Ϫ ) or the natriuretic peptide receptor-A gene (Npr1 Ϫ/Ϫ ) exhibit cardiac hypertrophy under resting conditions 3,5,11-13 and develop exaggerated hypertrophy after volume or pressure overload. 6,12,13 Furthermore, these studies raise the question as to whether variation in ANP response to hemodynamic stress is an important mediator of cardiac hypertrophy and remodeling in human hypertension and heart failure. Although studies in Nppa Ϫ/Ϫ mice have clearly demonstrated the adverse effect of ANP deletion on cardiac hypertrophy and remodeling, the effect of a modest ANP deficiency on the development of cardiac hypertrophy, remodeling, and failure remains unknown.ANP-heterozygous mice (Nppa) have normal blood pressure on either a normal-(0.5% NaCl) or an intermediate-salt (2% NaCl) diet, 6,14 in contrast to the hypertension observed in Nppa Ϫ/Ϫ mice under these conditions. 11 On a very-high-salt (8% NaCl) diet, however, Nppa ϩ/Ϫ mice develop hypertension. 6 The cardiac phenotype of the heterozygous ANP-knockout has not been rigorously studied under either basal or stress conditions. However, in their original report of this model, John et al 6 did not find a significant difference in cardiac weight between Nppa ϩ/ϩ and Nppa ϩ/Ϫ mice. The relatively normal cardiac phenotype in the heterozygous ANP-knockout might indicate...