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Biomedical subjects

N J Samani

Publications and source records attributed to N J Samani.

At least 91 records · Page 5Linked to original sources
PubMed1993

Failure of the heat-shock protein 70 locus to cosegregate with blood pressure in spontaneously hypertensive rat x Wistar-Kyoto rat cross.

OBJECTIVE: To investigate the involvement of the heat-shock protein 70 (hsp70) locus, located in the rat major histocompatibility complex (RT1), in hypertension of the spontaneously hypertensive rat (SHR). Previous studies have shown abnormal expression of hsp70 in the SHR and an association of the SHR hsp70 allele with increased blood pressure in recombinant inbred strains derived from a cross of SHR with Brown-Norway rats. DESIGN: SHR were crossed with normotensive Wistar-Kyoto (WKY) rats to produce a large cohort of F2 rats segregating for blood pressure and hsp70 alleles. Two hundred and thirty-three rats were maintained on a normal-salt diet and 167 were put on a high-salt diet (1% sodium chloride in drinking water) from 16 to 26 weeks of age. METHODS: Blood pressure was measured indirectly at 12, 16 and 20 weeks of age in rats on the normal-salt diet and at 16 (pre-salt), 18 and 20 weeks in rats on the high-salt diet. Both groups had direct conscious blood pressure measurements at 25-26 weeks of age. Genotyping was carried out for a BamH1 polymorphism in the hsp70 gene by Southern blotting. RESULTS: The hsp70 genotype had no effect on any of the blood pressure measurements in rats on either diet. CONCLUSIONS: We find no evidence of linkage between the hsp70 gene locus, and by implication other genes located within the rat RT1 complex, and blood pressure in our cross of SHR and WKY rats.

Animals↗
PubMed1993

A gene differentially expressed in the kidney of the spontaneously hypertensive rat cosegregates with increased blood pressure.

The role of the kidney in initiating hypertension has been much debated. Here we demonstrate that a recently identified gene of yet unknown function, termed SA, which is differentially expressed in the kidney of the spontaneously hypertensive rat, cosegregates with an increase in blood pressure in F2 rats derived from a cross of the spontaneously hypertensive rat with normotensive Wistar-Kyoto rats, accounting for 28 and 21% of the genetic variability in systolic and diastolic blood pressures, respectively. Further, the genotype at this locus appears to determine the level of expression of the gene in the kidney. The findings provide strong evidence for a primary genetic involvement of the kidney in hypertension.

Aging↗
PubMed1993

Vascular RAA system.

Biochemical and bioassay evidence has proved the existence of tissue RAA systems although their function has not been satisfactorily defined. There are two sources of tissue renin: uptake from plasma and local synthesis. The uptake system has been demonstrated in arterial tissue. Retention of renin can be demonstrated in the aortic wall and the presence of renin at this site is closely correlated with the persistent elevation of blood pressure. Renin gene expression can be demonstrated in several organs such as the liver, brain and arterial wall, although the function of renin or pro-renin at these sites is unknown. Intracellular angiotensin II receptors have been identified that play a role in regulating gene expression. In addition to raising vascular tone, angiotensin II generated in this way could have a trophic action upon cardiac and vascular structures. There is now very strong evidence in favour of the extrarenal RAA system having a pathogenetic role in some forms of hypertension. Renin gene polymorphisms co-segregate with blood pressure in some genetic models, despite normal or low plasma renin and incorporation of an additional mouse renin gene construct into the rat genome produces severe hypertension despite suppression of renal renin.

Biological Assay↗
PubMed1993

High blood pressure and metabolic disorders are associated in the Lyon hypertensive rat.

OBJECTIVE: A large population of F2 rats, obtained from a cross between male Lyon hypertensive (LH) rats and female Lyon normotensive (LN) rats, was studied in order to assess the relationship between increased body weight, hyperlipidaemia and high blood pressure which characterize LH rats. METHODS: Mean arterial pressure (MAP) was recorded in male, conscious, freely moving LH, LN, F1 and F2 rats aged 30 weeks. Plasma total cholesterol, high-density lipoprotein-, low-density lipoprotein- and very low-density lipoprotein-cholesterol, phospholipids, triglycerides, insulin and glucose were measured. RESULTS: In the F2 cohort it was observed that high MAP was a recessive trait that depends on several genes and was unrelated to body weight. The left ventricular weight, corrected for tibia length, was correlated with MAP. Plasma total and high-density lipoprotein-cholesterol and phospholipids concentrations were lower in the F1 rats than in the LN rats, suggesting an overdominance of the LN alleles. In the F2 rats MAP was related to total, high-density lipoprotein- and low-density lipoprotein-cholesterol. Plasma triglycerides, insulin and the insulin:glucose ratio, which were higher in the LH rats than in the LN rats, were also correlated with MAP in the F2 cohort. Using stepwise multiple regression analysis, MAP remained correlated with plasma total cholesterol, insulin and the insulin:glucose ratio, but not with triglycerides. CONCLUSIONS: Hypertension in LH rats is a recessive trait that is independent of body weight. In addition, the cosegregation of blood pressure with plasma cholesterol and, to a lesser degree, with insulin levels, which was observed in the present study provides the first direct evidence that these phenotypes are associated and are not due simply to genetic drift in the Lyon model.

Animals↗
PubMed1992

Transcutaneous ultrasound measurement of blood-flow in internal mammary artery to coronary artery grafts.

Transcutaneous doppler ultrasound was used to examine internal-mammary-artery (IMA) blood-flow in 26 patients with IMA coronary bypass grafts. The ungrafted right IMA could be seen in all of 19 patients, the grafted left IMA in 16 of 26, and the grafted right IMA in 3 of 7. The velocity profile recorded from the proximal part of the grafted IMA is distinct from that of an ungrafted artery, with a systolic peak which reflects graft capacitance in the face of high intramyocardial resistance, and a diastolic peak which represents graft conductance when intramyocardial resistance is low. Total graft blood-flow can be estimated from the mean velocity and the measured vessel diameter; resting flows ranged from 22 to 79 ml/min. In recently grafted patients, resting graft blood-flow correlated with myocardial "run-off" estimated from preoperative arteriograms; graft blood-flow increased appropriately with exercise. This simple, non-invasive technique to measure IMA graft blood-flow may find applications for routine postoperative follow-up of patients with IMA grafts and for studies on the physiology and pharmacology of coronary artery blood-flow.

Blood Flow Velocity↗
PubMed1991

Renal and extra-renal levels of renin mRNA in experimental hypertension.

1. Using a ribonuclease-protection assay, renin mRNA levels were compared in the kidneys, livers, brains, hearts and adrenal glands of two-kidney, one-clip Goldblatt hypertensive rats with those of age-matched control rats at 4 weeks ('early') and 20 weeks ('chronic') after clipping, and in the kidneys and adrenal glands of rats treated for 3 weeks with deoxycorticosterone and salt (deoxycorticosterone-salt hypertension) with those of control rats. 2. While marked changes were observed in kidney renin mRNA levels in all three experimental groups compared with their respective controls, in most of the extra-renal tissue studied minimal, if any, difference was seen in renin mRNA levels between the hypertensive and control rats. 3. The findings suggest that in these extra-renal tissues renin gene expression is differently regulated from that in the kidney, and particularly that it is not profoundly affected by changes in the level of circulating angiotensin II. 4. An increase in renin mRNA was observed in the adrenal glands of the 'chronic' Goldblatt rats, which may be of relevance to the maintenance of hypertension in this model.

Adrenal Glands↗
PubMed1991

The role of extrarenal renin in Goldblatt hypertension.

Renin-like activity can be demonstrated in arterial extracts from normal rats and from rats with Goldblatt hypertension. We have found no evidence, however, for elevated arterial renin levels in relation to plasma renin activity. Studies of the reversal of renovascular hypertension indicate that the fall in blood pressure produced by renal artery deconstriction is not renin-dependent. However, molecular biological techniques indicate that extrarenal renin gene expression is altered in some tissues, such as the adrenal gland in Goldblatt hypertension, and it is possible therefore that extrarenal renin synthesis is important in blood pressure control. This has to be distinguished from renin derived from plasma uptake.

Animals↗
PubMed1991

Molecular biology of the vascular renin-angiotensin system.

Considerable evidence has been accumulated for a renin-angiotensin system in the blood vessel wall with local generation of both angiotensin I and angiotensin II that plays an important role in blood pressure regulation. A major source for vascular renin is renal renin taken up by the arterial wall from the circulation. However, recent studies suggest that, in addition, local synthesis of components of the renin-angiotensin cascade also takes place in the vessel wall. The contribution that these locally derived components make to the functions of the vascular renin-angiotensin system remains to be elucidated. Studies, particularly in vitro, suggest that vascular pathways for angiotensin generation not involving renin or angiotensin-converting enzyme may also exist. As in the case of the locally derived components of the renin-angiotensin cascade, the role of these alternate pathways in the physiology of the vascular wall remain to be defined.

Angiotensin II↗
PubMed1991

Molecular biology of the renin-angiotensin system: implications for hypertension and beyond.

In the last decade, nucleic acid sequences coding for all three components of the renin-angiotensin cascade have been cloned. This has led to increased understanding of the transcriptional and translational regulation of renin, angiotensinogen, and angiotensin-converting enzyme (ACE). This review discusses the impact of the availability of these clones in three clinically relevant areas--the role of the renin-angiotensin system in hypertension, the role of tissue renin-angiotensin systems, and the development of renin inhibitors.

Animals↗
PubMed1990

Vascular renin and hypertension. Uptake versus synthesis.

Conventional radioimmunoassay techniques demonstrated in the aortic wall a renin-like activity which is derived from plasma but has a longer half-life than plasma renin. Blood pressure elevation after renin injection into nephrectomized rats correlates better with aortic renin than with plasma renin. Vascular and other extrarenal tissue can also synthesize renin. Using a ribonuclease protection technique for the detection of renin messenger RNA we have been able to demonstrate that a wide variety of extrarenal tissues contain the renin message. In at least two of these, the brain and the liver, renin messenger RNA levels are unaffected by changes in dietary salt or by changes in systemic blood pressure. Functional studies using isolated human resistance vessels also demonstrate the presence of renin-like activity by a contractile response to added renin substrate. It is suggested that extrarenal tissues therefore contain renin-like activity derived both from uptake and from local synthesis. These systems may be regulated in different ways and may carry out different functions.

Animals↗
PubMed1990

Analysis of the renin gene intron A tandem repeat region of Milan and Lyon hypertensive rat strains.

The region of intron A of the rat renin gene containing a unique tandemly repeated sequence was analysed in the Milan and Lyon hypertensive rat strains and their controls, and in several Sprague-Dawley rats, using an oligonucleotide probe complementary to the tandemly repeated sequence and a renin complementary DNA probe. In the Milan rats, the size of the Bgl II DNA fragment encompassing the tandem repeat region was the same in the hypertensive (MHS) and normotensive (MNS) strains. In the Lyon model, a difference of 1.1 kilobase (equivalent to about 28 copies of the 38 basepair tandem repeat sequence) was observed in the size of the Bgl II fragment of the hypertensive (LH) and normotensive (LN) strains. However, the finding that the size of the fragment in the Lyon low-blood-pressure (LL) strain was the same as that in the LH strain rather than the LN strain suggests that the difference between the two latter strains is not by itself a major cause of the blood pressure difference between them in the intron A tandem region. An analysis of Sprague-Dawley rats, from which the Lyon strains are derived, showed that at least three different renin gene alleles, two with Bgl II fragments of the same size as those seen in the Lyon strains, are randomly segregating in this population.

Alleles↗
PubMed1989

The renin gene in patients with malignant hypertension and raised plasma renin activity.

1. We have examined the hypothesis that the raised plasma renin activity in patients with malignant hypertension without an underlying cause is the consequence of expression of a duplicate renin gene. 2. DNA extracted from leucocytes of patients with malignant hypertension and of normotensive controls was digested with the restriction endonuclease PstI and hybridized with a radioactively labelled human renin complementary DNA probe. As an internal control the DNA was concurrently hybridized with a human c-myc protooncogene probe. 3. The signals for each subject from the two probes were quantitatively compared by densitometry. 4. There was no evidence of duplication of the renin gene in the patients with malignant hypertension.

Adult↗
PubMed1989

A widespread abnormality of renin gene expression in the spontaneously hypertensive rat: modulation in some tissues with the development of hypertension.

1. Renin messenger RNA (mRNA) levels were compared in the kidneys, livers, brains, adrenals, aortae and hearts of spontaneously hypertensive (SHR) and Wistar-Kyoto (WKY) rats at 5 and 12 weeks of age using a ribonuclease-protection technique. 2. Relative levels of renin mRNA were increased in the kidney, liver, brain, adrenal and heart of the young SHR compared with the WKY. In the aorta, levels were similar in the two strains at 5 weeks. 3. In 12-week-old animals, while increased levels persisted in the liver, brain and adrenal of the SHR, the level in the kidney was now the same in the two strains and the levels in the heart and aorta were lower in the SHR compared with the WKY. 4. Renin mRNA levels in the kidneys of SHR and WKY were also compared by Northern blotting and confirmed the observations made with the ribonuclease-protection technique. 5. The findings indicate a widespread abnormality of renin gene expression in the SHR which is modulated in some tissues by the development of hypertension. 6. While the mechanism(s) for the abnormality remains to be determined, the increased renin mRNA levels in the SHR in several tissues concerned with blood pressure regulation suggests an important role for the renin-angiotensin system in the development and maintenance of hypertension. 7. However, the finding of increased renin mRNA in the liver also suggests abnormalities in other, as yet unknown, functions of the renin-angiotensin system in the SHR.

Adrenal Glands↗