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N J Samani

Publications and source records attributed to N J Samani.

At least 73 records · Page 4Linked to original sources
PubMed1995

Insertion/deletion polymorphism in the angiotensin-converting enzyme gene and risk of restenosis after coronary angioplasty.

Early restenosis in over 30% of cases limits the benefits of percutaneous transluminal coronary angioplasty (PTCA). The mechanisms that underlie restenosis are uncertain, although experimental evidence suggests that the renin-angiotensin system is involved in the vascular response to angioplasty. An insertion(I)/deletion(D) polymorphism in the angiotensin-converting enzyme (ACE) gene, which influences plasma ACE level, has been associated with an increased risk of myocardial infarction in those with the DD genotype. To investigate whether this polymorphism influences the risk of restenosis after PTCA, 233 patients who underwent single-vessel angioplasty in the Subcutaneous Heparin and Angioplasty Restenosis Prevention (SHARP) study were genotyped for the I/D polymorphism and pre-PTCA, post-PTCA, and 4-month clinical and quantitative angiographic data were compared in the three genotype groups. The groups, (II 53, ID 117, and DD 63) were well matched for baseline clinical and both pre- and post-PTCA angiographic features. At 4-month follow-up there was no significant difference between the genotype groups with respect to any of the quantitative angiographic criteria of restenosis: minimal luminal diameter at the site of the angioplasty (DD 1.35 [SE 0.10] mm, ID/II 1.43 [0.05] mm, difference -0.08 [95% CI -0.30 to 0.14]), numbers of subjects with more than 50% diameter stenosis (DD 49%, ID/II 46%, relative risk 1.06 [0.79 to 1.43]), or the number of subjects with more than 50% loss of the acute diameter gain after PTCA (DD 54%, ID/II 43%, 1.26 [0.94 to 1.67]). Likewise, there was no difference in the number of subjects with angina or a positive exercise stress test. We conclude that, in patients undergoing elective PTCA, the I/D polymorphism in the ACE gene does not influence the extent of restenosis, and typing for the polymorphism will not be a useful predictor of risk before the procedure.

Adult↗
PubMed1995

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

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)

Coronary Disease↗
PubMed1995

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

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.

Adult↗
PubMed1995

Analysis of the role of angiotensinogen in spontaneous hypertension.

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 F2 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.

Angiotensinogen↗
PubMed1995

SA gene and hypertension.

The SA 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 SA gene from the SHR and several other genetically hypertensive strains was found to cosegregate with increased blood pressure in F2 progeny derived from crosses with normotensive rats. The increased expression of the SA 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) SA represents a major component of an important novel system regulating blood pressure, and (ii) it underlies a primary renal mechanism predisposing to hypertension.

Animals↗
PubMed1994

Chromosomal assignment of the human SA gene to 16p13.11 and demonstration of its expression in the kidney.

The SA gene is a novel gene of yet unknown function recently implicated in blood pressure regulation in rodent models of genetic hypertension. In this study we have located the human homologue of the SA gene to chromosome 16p13.11, by a combination of fluorescence in-situ hybridization and analysis of somatic cell hybrids carrying different segments of chromosome 16. This should facilitate investigation of its role in the genetic tendency to hypertension in humans. Increased expression of the gene in the kidney may be the mechanism through which some allelic variants of the gene raise blood pressure in rodent models. In this study we also demonstrate that the SA gene is expressed in human kidneys.

Animals↗
PubMed1994

Transient reversal of blood flow in an internal thoracic artery to coronary artery graft during syncope.

Transcutaneous duplex ultrasound can be used to image and quantify blood flow in the proximal part of the internal thoracic artery to coronary artery bypass grafts. In addition to providing information about graft patency and blood flow for follow-up purposes, the technique also provides an opportunity to study the physiology and pharmacology of the coronary circulation. In this paper we describe and attempt to interpret an unusual pattern of internal thoracic artery graft blood flow observed during inadvertent nitrate-induced syncope.

Coronary Artery Bypass↗
PubMed1994

The rat SA gene shows genotype-dependent tissue-specific expression.

1. SA is a recently identified gene implicated in blood pressure regulation in rodent models of genetic hypertension. In this study we have examined, by Northern blotting, its expression in tissues of the spontaneously hypertensive rat, the Wistar-Kyoto rat and F2 rats, derived from a cross of the spontaneously hypertensive rat with the Wistar-Kyoto rat. 2. We demonstrate that the gene is expressed in a tissue-specific manner. Expression was detected in four sites: kidney, liver, brain and testes. 3. In the kidney and liver expression was higher in the spontaneously hypertensive rat than in the Wistar-Kyoto rat, whereas in the brain and testes the pattern was reversed. 4. In the F2 rats, the levels of SA mRNA in the liver, brain and testes were found to be primarily determined by the genotype at the SA gene locus. 5. The findings suggest the presence of strain-specific cis- and more than one tissue-specific trans-acting factors regulating the expression of the rat SA gene.

Animals↗
PubMed1994

Molecular genetics of susceptibility to the development of hypertension.

Blood pressure is a quantitative multifactorial trait with both environmental and genetic determinants, with essential hypertension simply representing one extreme of the blood pressure distribution. While much is known about environmental factors that predispose to the development of hypertension, the nature of the genetic factors that increase such susceptibility remain virtually unknown. However, with advances in molecular techniques, several loci that influence blood pressure in rodents have been identified and recently in two selected sets of human hypertensives, a molecular variant at the angiotensinogen locus has been linked to the tendency to hypertension. It is likely that in the next few years several genetic determinants of blood pressure variability in humans will be identified. Such information will not only increase our understanding of the pathophysiology of hypertension and identify novel treatments but may permit preventative and therapeutic measures to be targetted more specifically than at present.

Animals↗
PubMed1994

Transcutaneous ultrasound assessment of internal thoracic artery to coronary artery grafts in patients with and without ischaemic symptoms.

OBJECTIVE: To evaluate transcutaneous duplex ultrasound in the assessment of internal thoracic artery to coronary artery grafts. SETTING: Regional cardiothoracic centre. METHODS: Prospective duplex ultrasound evaluation of 83 consecutive patients undergoing left internal thoracic artery to coronary artery grafts, together with combined angiographic and duplex ultrasound evaluation of 17 patients with suspected recurrent myocardial ischaemia after internal thoracic artery grafting. RESULTS: The grafted internal thoracic artery was imaged in 65 (78%) of 83 consecutive postoperative patients, and in 13 (75%) of 17 patients with suspected graft dysfunction. Grafts were recognised by their characteristic position and biphasic blood flow pattern. Resting graft flow was estimated from the time averaged velocity and graft cross sectional area. Median resting flow in patients without ischaemic symptoms was 36 ml/min (interquartile range 24 to 49 ml/min). Of 13 patients with recurrent ischaemia in whom the graft could be imaged, nine patients with estimated flow in the lowest quartile or abnormal flow profiles, or both, had graft disease or anastomotic problems on angiography, while four with satisfactory graft flow on ultrasound examination had normal graft flow on angiography, but had evidence of native disease progression in other vessels. Two of four patients in whom it was not possible to image the graft on ultrasound had satisfactory graft function on angiography. CONCLUSIONS: For those patients whose internal thoracic artery graft can be imaged, transcutaneous duplex ultrasound is a helpful non-invasive guide to graft function. The main limitations to the technique are an inability to image the graft in about 20% of patients, and possible inaccuracy in estimating graft diameter.

Coronary Artery Bypass↗
PubMed1994

Expression of components of the RAS during prolonged blockade at different levels in primates.

To assess the effects of inhibition of the renin-angiotensin system at different levels on plasma concentrations of components of the system and on renin and angiotensinogen gene expression, marmosets on a low-sodium diet were treated for 1 wk by continuous intraperitoneal infusion with either the renin inhibitor CGP-29287, the ACE inhibitor benazeprilat, the angiotensin II antagonist valsartan, the renin inhibitory monoclonal antibody R-3-36-16, or vehicle. Plasma total immunoreactive renin increased (14- to 20-fold) after all three modes of interference. Plasma angiotensinogen was significantly reduced in the benazeprilat- and valsartan-treated marmosets but not in the CGP-29287-treated animals. Plasma concentration of angiotensin II was significantly decreased in the benazeprilat-, CGP-29287-, and R-3-36-16-treated marmosets and was increased in the valsartan-treated marmosets. Kidney renin mRNA level increased 8- to 15-fold in all groups. Hepatic angiotensinogen mRNA level increased with CGP-29287 treatment but decreased with the other treatments. Kidney angiotensinogen mRNA level was not affected by any treatment. Different modes of inhibition of the renin-angiotensin system have different effects on plasma components of the system and liver angiotensinogen expression.

Angiotensin II↗
PubMed1994

Hypertension in the spontaneously hypertensive rat and the sex chromosomes.

We investigated the involvement of loci on the sex chromosomes in the hypertension of the spontaneously hypertensive rat (SHR) by studying male F1 and F2 generation rats derived from reciprocal crosses of SHR with Wistar-Kyoto (WKY) rats (cross 1: WKY female x SHR male; cross 2: SHR female x WKY male). At 16 weeks of age there was no significant difference in the blood pressures of F1 animals derived from the two crosses. Similarly, in the F2 generation there was no significant difference in either indirect blood pressures measured at 12, 16, or 20 weeks of age or in direct systolic and diastolic blood pressures measured at 25 weeks of age between animals derived from the two crosses maintained on a normal salt diet. In a second study, cohorts of F2 rats from the two crosses were given 1% salt in their drinking water for 10 weeks from 16 weeks of age with indirect blood pressure measurements at 16 (presalt), 18, and 20 weeks and direct blood pressure measurements at 26 weeks. Although overall these animals had significantly higher blood pressures at both 20 and 26 weeks than animals of the first study, again there was no difference in blood pressures of animals derived from the two crosses, apart from a marginally significantly higher blood pressure at 18 weeks in animals from cross 1 (with SHR grandfather). The findings indicate that the sex chromosomes of the SHR and WKY rat used in these crosses do not contain loci where alleles differentially influence blood pressure under the genetic milieu provided by the cross.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1994

Early narrowed afferent arteriole is a contributor to the development of hypertension.

The kidney is probably critically involved in the development of essential hypertension, as in many genetic models of hypertension. We have investigated whether a narrowed renal afferent arteriole is involved in the pathogenesis of hypertension in spontaneously hypertensive rats. Systolic blood pressure of 37 F2 generation spontaneously hypertensive rats/Wistar-Kyoto rats was measured at age 7 weeks. The right kidney was removed, and lumen diameter and media cross-sectional area of the afferent arterioles were measured after having been fixed while relaxed and under a transmural pressure of 100 mm Hg. The uninephrectomized rats continued until age 23 weeks, when mean blood pressure was measured. Mean blood pressure at 23 weeks was negatively correlated with lumen diameter at 7 weeks. Quartile analysis based on lumen diameter at 7 weeks showed that compared with rats in the top lumen diameter quartile, rats in the bottom lumen diameter quartile had a reduced media cross-sectional area at 7 weeks (17%), the same systolic blood pressure at 7 weeks, and an increased (16%) mean blood pressure at 23 weeks. We conclude that in spontaneously hypertensive rats a narrowed lumen of distal afferent arterioles at 7 weeks contributes to later development of increased blood pressure. This reduced lumen could be caused by inhibited renal afferent arteriole growth.

Aging↗
PubMed1994

Increased expression of the SA gene in the kidney of the spontaneously hypertensive rat is localized to the proximal tubule.

OBJECTIVE: To identify the site of the increased expression of the SA gene in the kidney of the spontaneously hypertensive rat (SHR) compared with the Wistar-Kyoto (WKY) rat. METHODS: In situ hybridization of SHR and WKY rat kidney sections with a radioactively labelled rat SA complementary DNA probe. RESULTS: Compared with WKY rat kidney sections, the probe bound intensely to the SHR renal cortex. Binding was sensitive to pretreatment of the section with RNAase A. Microscopic examination after autoradiography showed the increased signal in the SHR to be localized over proximal tubules. Background signal was observed over glomeruli, distal tubules, interlobular arteries and afferent arterioles. CONCLUSIONS: The localization of the increased expression of the SA gene in the SHR kidney compared with the WKY rat kidney to the proximal tubule suggests that it might influence blood pressure through effects on tubular function. Several differences in proximal tubular function have already been described between the SHR and WKY rat, and the relationship of these to tubular SA gene expression now need to be investigated. However, in the absence of any known functions for the SA gene product it is also possible that it might act through entirely novel, still undefined mechanisms.

Animals↗
PubMed1994

Ventricular aneurysmectomy: indications, operative findings and outcome at a single centre.

We assessed all patients (n = 120) who underwent left ventricular aneurysmectomy as part of a cardiac surgical procedure at the Groby Road Hospital subregional cardiothoracic centre (1980-1990). Of these, 71% had had only one prior myocardial infarction and 84% had symptoms generally associated with aneurysms (congestive cardiac failure, ventricular arrythmias or systemic embolism). The indication for surgery was a combination of angina and aneurysm-related symptoms in 43%, one or more aneurysm-related symptoms in 35%, and angina alone in 22%. The majority of patients (57%) underwent aneurysmectomy and coronary artery bypass grafting, although 35% underwent aneurysmectomy alone. Most (61%) aneurysms were > 6 cm in size, and 75% were located at the apex of the left ventricle. Forty per cent had a mural thrombus, and there was no relationship between prior warfarin use and occurrence of mural thrombus. Overall perioperative mortality was 17% (20 patients), although mortality halved between the first and second halves of the study period. The main reason for perioperative was pump failure. Seventeen patients died late during follow-up (mean 52.5 months), the main cause being further myocardial infarction. Nevertheless, 65% were still alive at 5 years, and 81% and 66% of survivors were still better than pre-operatively at 5 and 8 years, respectively. Post-operative improvement was equally as good in patients who underwent aneurysmectomy alone, or those operated on for aneurysm-related symptoms, as in the whole group. In logistic regression analysis, the only predictor of adverse long-term outcome was the number of previous myocardial infarctions.(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗
PubMed1993

Genetic determinants of diastolic and pulse pressure map to different loci in Lyon hypertensive rats.

Several genetic loci involved in blood pressure regulation have recently been localized in experimental models of hypertension, but the manner in which they influence blood pressure remains unknown. Here, we report a study of the Lyon hypertensive rat strain showing that different loci are involved in the regulation of steady-state (diastolic pressure) and pulsatile (systolic-diastolic, or pulse pressure) components of blood pressure. Significant linkage was established between diastolic blood pressure and a microsatellite marker of the renin gene (REN) on rat chromosome 13, and between pulse pressure and the carboxypeptidase B gene (CPB) on chromosome 2. These findings show that two independent loci influence different haemodynamic components of blood pressure, and that pulse pressure has a specific genetic determination.

Analysis of Variance↗
PubMed1993

When should we diagnose incomplete right bundle branch block?

An rSr' pattern with QRS duration of less than 0.12 s in the right precordial leads can be due to incomplete right bundle branch block (which may progress to complete right bundle branch block) or can be a normal electrophysiological variant. To identify other ECG features that may help to distinguish between these two possibilities, ECGs of 15 patients who progressed from normal to complete right bundle branch block through an intermediate rSr' pattern of incomplete right bundle branch block were analysed. The following features in the right precordial leads (V1, V2) that preceded or accompanied the appearance of the rSr' were identified: diminution of the S wave depth (100%), inversion of ratio of the S wave depth to SV1 > SV2 (93%), slurring of the downstroke or upstroke of the S wave (27%) and prolongation of the QRS duration to > or = 0.10 s (73%). When a further 79 subjects with rSr' pattern in the right precordial leads and QRS duration of < 0.12 s were divided into those with SV1/SV2 ratio > 1.0 and those with SV1/SV2 < 1.0, compared with the latter the subjects with SV1/SV2 ratio > 1.0 were found to be significantly older (59.8 +/- 18.4 years vs 32.8 +/- 18.1 years, P < 0.001), to exclusively show S wave slurring (37% vs 0%), and to more likely have a QRS duration > or = 0.10 s (74% vs 7%).(ABSTRACT TRUNCATED AT 250 WORDS)

Adult↗