Showing papers by "Nilesh J. Samani published in 1995"

Analysis of the Role of Angiotensinogen in Spontaneous Hypertension

Abstract: Allelic variants at the human angiotensinogen locus have recently been reported to increase susceptibility to the development of essential hypertension. In this study we analyzed the role played by angiotensinogen in the elevated blood pressure of the spontaneously hypertensive rat (SHR). The SHR angiotensinogen locus (on chromosome 19) cosegregated with a significant ( P =.003) and specific increase in pulse pressure in F 2 rats derived from a cross of the SHR with the normotensive Wistar-Kyoto rat (WKY), accounting for 20% of the genetic (10% of total) variance in this phenotype. To identify potential mechanisms underlying the effect of the locus, we further examined angiotensinogen structure and expression in the two strains. Sequence analysis of the respective coding regions revealed no differences in the primary structure of angiotensinogen between the strains. Likewise, plasma angiotensinogen level did not differ in adult rats of the two strains. However, gene expression studies showed tissue-specific, age-related differences in angiotensinogen mRNA levels between SHR and WKY, particularly in the aorta. The findings suggest that pulse pressure, which significantly influences cardiovascular risk, has independent genetic determinants. They further suggest that the effect of the angiotensinogen locus on this phenotype in the SHR may be mediated through a tissue-specific abnormality of angiotensinogen gene expression.

The SA gene : predisposition to hypertension and renal function in man

Abstract: 1. The SA gene is expressed in the kidneys and is associated with hypertension in man and experimental animal models. Predisposition to hypertension is associated with renal haemodynamic abnormalities and increased renal SA gene expression. 2. We studied the distribution of the SA gene alleles (A1, A2), defined by the PstI polymorphism, in young adults with contrasting predisposition to hypertension to determine whether genetic variation at the SA gene locus is associated with variations in renal haemodynamics, electrolyte metabolism and the renin-angiotensin system. 3. The frequency of the A2 allele was not significantly different between subjects with high personal and parental blood pressures and subjects with low personal and parental blood pressures. We detected no overall relationship between blood pressures and SA genotype, even after taking sodium intake into account. 4. Glomerular filtration rate, renal blood flow, renal vascular resistance, plasma volume, exchangeable sodium and total body water did not differ according to SA genotypes. Moreover, we detected no significant effect of SA genotype on circulating components of the renin-angiotensin system or atrial natriuretic peptide. 5. In our population, genetic variation at the SA gene locus defined by PstI polymorphism does not influence the renal characteristics that contribute to the development of hypertension.

Effects of exercise and nitrates on blood flow in internal mammary artery to coronary artery grafts: a non-invasive study.

Abstract: 1. The aim of the present study was to investigate the effects of exercise and of sublingual glyceryl trinitrate on the pattern of blood flow, as studied by Doppler ultrasound, in internal mammary artery grafts performed to relieve severe stenosis of the left anterior descending coronary artery. The accessibility of the graft to transcutaneous ultrasound examination allows the effects of exercise and nitrate administration on coronary blood flow to be studied non-invasively. 2. Angina-free patients with left internal mammary to left anterior descending coronary artery grafts were studied using transcutaneous duplex ultrasound at rest, after leg exercise and after sublingual administration of 0.5 mg or 1 mg of glyceryl trinitrate. 3. Resting graft blood flow showed a biphasic pattern, with forward flow in both systole and diastole. Exercise caused an increase in time-averaged velocity of graft blood flow from 17.3 (3.3) to 24.0 (7.2) cm/s (P = 0.001), and of calculated volume flow from 44.7 (3.08) to 59.8 (5.89) ml/min (P = 0.002). Diastolic peak velocity increased from 36.1 (9.9) cm/s to 46.8 (16.2) cm/s (P = 0.04), while peak systolic velocity was unchanged. Nitrate administration caused a fall in systolic and diastolic blood pressure and an increase in heart rate; graft flow was maintained [time-averaged velocity 18.3 (6.2) cm/s before and 16.7 (5.7) cm/s after 500 micrograms of glyceryl trinitrate], but systole was shortened and the proportion of blood flow in diastole increased [systolic/diastolic flow ratio 0.558 (0.139) before and 0.374 (0.156) after 500 micrograms of glyceryl trinitrate, P = 0.01].(ABSTRACT TRUNCATED AT 250 WORDS)

SA gene and hypertension.

Abstract: The S A gene was initially identified by differential hybridisation because of its higher expression in the kidney of the spontaneously hypertensive rat (SHR) compared with the normotensive Wistar-Kyoto rat. In subsequent studies, the allele of the S A gene from the SHR and several other genetically hypertensive strains was found to cosegregate with increased blood pressure in F 2 progeny derived from crosses with normotensive rats. The increased expression of the S A gene in the kidney of the SHR occurs early, before the rapid rise in blood pressure in this model, is genotype-dependent and localised to the proximal tubule. Although the functions of its protein product remain to be elucidated, these findings raise the exciting possibilities that : (i) S A represents a major component of an important novel system regulating blood pressure, and (ii) it underlies a primary renal mechanism predisposing to hypertension.