Search PubMed⌕ Search

Biomedical subjects

N J Samani

Publications and source records attributed to N J Samani.

At least 19 recordsLinked to original sources
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↗
PubMed1989

DNA fingerprinting of spontaneously hypertensive and Wistar-Kyoto rats: implications for hypertension research.

Probes to hypervariable minisatellite regions of DNA identify multiple loci scattered over the autosomal chromosomes and produce a complex Southern blot pattern of fragments termed a DNA 'fingerprint'. As concern has been raised that different stocks of spontaneously hypertensive rats (SHR) and Wistar-Kyoto rats (WKY) may not be biologically identical, we have compared the DNA of SHR and WKY from several sources using two such probes which identify different sets of minisatellite sequences. While the DNA fingerprints of SHR from the various sources were identical, variability was observed in those of WKY, indicating genetic heterogeneity between different WKY stocks. In animals from one of the commercial suppliers even inter-rat variability in DNA fingerprints was seen, suggesting genetic heterogeneity within that single colony. These observations indicate that experimental results obtained using WKY from different sources may not be directly comparable and could provide an explanation for some of the conflicting data that exist on the comparative characteristics of SHR and WKY. In separate studies, direct comparisons both of the DNA fingerprints of SHR and WKY and of SHR and stroke-prone spontaneously hypertensive rats (SHRSP) showed multiple differences between the strains. The polymorphisms seen could provide useful linkage markers in locating the chromosomal sites of the genetic loci responsible for raised blood pressure in the SHR and the propensity to strokes in the SHRSP.

Animals↗
PubMed1989

Modulation of mouse renin gene expression by dietary sodium chloride intake in one-gene, two-gene and transgenic animals.

We have studied the effect of dietary NaCl loading on renin gene expression in one-gene, two-gene and transgenic mouse strains. By Northern blotting, we found an approximate twofold reduction in renin messenger (m) RNA in the kidneys of high-NaCl-treated compared with low-NaCl-treated animals. Using an RNase-protection assay designed to discriminate between the different renin gene transcripts, we have shown that renin mRNAs derived from the Ren-1C gene of one-gene strains and the Ren-1D and Ren-2 genes of two-gene animals are all NaCl-responsive. Renin mRNA derived from a 19 kilobase Ren-1D transgene is also NaCl-responsive.

Animals↗
PubMed1989

Kidney renin mRNA levels in the early and chronic phases of two-kidney, one clip hypertension in the rat.

The effect of clipping the left renal artery on left and right kidney renin mRNA levels during the early and chronic phases of two-kidney, one clip Goldblatt hypertension in the rat was studied. Renin mRNA levels were determined using northern and dot blotting. Four weeks after clipping, renin mRNA levels were sixfold higher in the left kidney and eightfold lower in the right kidney of the Goldblatt rats compared with the left kidney of the sham-operated rats. Similar analysis at 20 weeks after clipping showed a fourfold increase in the left kidney and a 16-fold suppression in the right kidney compared with age-matched sham-operated control rats. The study demonstrates the profound changes that occur in renin gene expression in the clipped and contralateral kidneys in this model of hypertension and shows that these changes persist into the chronic phase of the hypertension.

Animals↗
PubMed1989

A major structural abnormality in the renin gene of the spontaneously hypertensive rat.

The renin genes of the spontaneously hypertensive rat (SHR) and Wistar-Kyoto (WKY) rat were compared by Southern blotting using cDNA and oligonucleotide probes. A 'deletion' of approximately 650 base pairs was found in the first intron (intron A) of the SHR gene compared with the WKY gene. Our studies strongly suggest that this is due to a decrease in the number of copies of the tandemly repeated sequence present within intron A of the rat renin gene. In both SHR and WKY, this region of the gene was found to be different from that of the parent Wistar rat and those of other Wistar-based inbred strains. The functional significance of the abnormality and any role it may have in hypertension in the SHR remain to be determined.

Animals↗
PubMed1989

Localisation and physiological effects of tissue renin-angiotensin systems.

Evidence suggests that the tissue renin-angiotensin-aldosterone (RAA) systems play an important role in BP homeostasis, with the possible importance of the vascular RAA system in hypertension being of particular interest. Although angiotensin II has a direct vasoconstrictor action, local production of angiotensin II may also be important in the control of sympathetic neurotransmission and in smooth muscle hyperplasia. Whilst renin-like activity can be demonstrated in arterial walls, the source of this is still uncertain. Uptake of renally derived plasma renin can be demonstrated, but local synthesis of biologically significant quantities of renin cannot be excluded by conventional assay methods. Recent studies of renin gene expression demonstrate the presence of renin mRNA in the arterial wall, liver, adrenal gland, heart and brain. The reduction of BP by ACE inhibitors, even when plasma renin activity is not elevated, has not been explained by an action on a local system and previous research efforts have focused on demonstrating renin-like activity in extra-renal tissues. However it is now possible to study those control systems which regulate the extra-renal RAA system. We have demonstrated a qualitative difference between plasma renin taken up by the arterial wall and renin gene expression (as an indicator of local renin synthesis). Unlike circulating renin, local extra-renal renin gene expression is not influenced by sodium balance or by feedback inhibition as a result of high renin levels. Locally generated angiotensin II derived from locally synthesised renin may therefore perform a different function from that of the circulating RAA system in vascular control.(ABSTRACT TRUNCATED AT 250 WORDS)

Animals↗
PubMed1988

Expression of the renin gene in extra-renal tissues of the rat.

Expression of the renin gene in several rat organs is demonstrated by the detection of renin mRNA using a ribonuclease-protection technique. In two of these sites, the brain and the liver, renin mRNA levels are unaffected by changes in dietary salt which markedly affect renal renin mRNA levels. The findings provide the basis for an important ubiquitous local regulatory role for the renin-angiotensin system extending beyond the circulation.

Animals↗