Search PubMed⌕ Search

Biomedical subjects

N J Samani

Publications and source records attributed to N J Samani.

101 records · Page 6Linked to original sources
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↗
PubMed1988

Histochemical localization of IGF-I and IGF-II mRNA in the rat between birth and adulthood.

We describe the postnatal ontogeny and localization of insulin-like growth factors I and II (IGF-I and -II) in the rat. We have used oligodeoxyribonucleotide probes for in situ hybridization (hybridization histochemistry) and for Northern blotting. IGF-II mRNA is strongly expressed in liver, skeletal muscle, perichondrium, leptomeninges and choroid plexus of the newborn. Demonstrable levels fall dramatically in the liver at 18-20 days postnatally but persist for longer periods in muscle and remain undiminished throughout life in the pia/choroid plexus, indicating that different control mechanisms operate in these tissues. IGF-I mRNA is predominantly found in the liver. Its level in this organ rises well before levels of IGF-II fall. This suggests that distinct factors govern the expression of IGF-I and -II genes.

Animals↗
PubMed1988

Control of IGF-II mRNA levels by glucocorticoids in the neonatal rat.

Insulin-like growth factor-II (IGF-II) is thought to be a major growth factor during fetal and neonatal development. Levels of IGF-II mRNA fall dramatically in the liver - the major site of endocrine production - between 18 and 20 days post-natally. No information concerning the control of gene expression post-natally has hitherto been available. Using Northern blotting and in-situ hybridization, we show here that cortisone acetate rapidly extinguishes IGF-II mRNA expression in the neonatal rat liver. The effect at putative autocrine/paracrine locations such as skeletal muscle and choroid plexus is much less marked or absent. The repression by cortisone acetate is discussed in the light of the available IGF-II gene sequence.

Animals↗
PubMed1987

Detection of renin messenger RNA in rat tissues: increased sensitivity using an RNAse protection technique.

Total cellular RNA and poly A+ RNA isolated from various tissues of Wistar-Kyoto (WKY) rats were screened for renin-specific messenger RNA by Northern blotting and RNAse protection. Northern blot analysis, carried out with a copy DNA (cDNA) probe of mouse submandibular gland renin, demonstrated a single RNA species of 1.8 kb in the kidneys of WKY rats. Other tissues screened by this technique were negative. With the more sensitive RNAse protection technique, our initial results indicate more widespread expression of renin, messenger RNA (mRNA) being detected in aorta, adrenal, heart, lung and spleen.

Adrenal Glands↗
PubMed1987

Histochemical localization of IGF-I and -II mRNA in the developing rat embryo.

We describe the histological localization of embryonic and fetal tissues whose cells express the genes coding for insulin-like growth factors I and II (IGF-I and IGF-II) in the developing rat. Our studies span the period between early somite stages and full term. We have used oligodeoxyribonucleotide probes and obtained results which are both topographically precise and highly reproducible. The gene coding for IGF-II is predominant throughout development. It is strongly expressed in the liver and yolk sac. A variety of other tissues also expresses the IGF-II gene, especially many mesodermally derived structures in the process of differentiation. Many tissues do not express IGF genes. Thus no IGF mRNA was demonstrable in ectodermally derived structures, including the central and peripheral nervous systems as well as the skin and its derivatives.

Animals↗