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Biomedical subjects

M R Rao

Publications and source records attributed to M R Rao.

At least 73 records · Page 4Linked to original sources
PubMed1996

[Effects of enalapril and taurine on left ventricular hypertrophy and arrhythmia in renovascular hypertensive rat].

The effects of enalpril (Ena, 6 mg.kg-1) and taurine (Tau, 30 mg.kg-1) on left ventricular hypertrophy (LVH) and ventricular arrhythmia were studied in two-kidney, one clip renovascular hypertensive rats (RHR). From the 9th week after operation, Ena and Tau were given per oral daily for 9 weeks. These drugs significantly decreased the systolic arterial pressure and the weight of the left ventricle. Combination of both drugs was found to reduce the blood pressure further than either drug used alone. Arrhythmias induced by trains of electrical stimuli were more frequent in working hearts isolated from RHR than that from normotensive rats. Ena and Tau could decrease the incidence of this arrhythmias in RHR. The calcium content in the myocardial mitochondria in RHR was increased compared with that in normotensive rats. Treatment with Ena and Tau reduced this increase significantly. These results suggest that chronic therapy with Ena and Tau can induce an attenuation of systemic arterial pressure and reduce the propensity of RHR heart to arrhythmogenesis by limiting cardiac hypertrophy and calcium overload of the myocardium.

Angiotensin-Converting Enzyme Inhibitors↗
PubMed1996

[Effects of m-Nif and Nif on left ventricle hypertrophy in rats induced by partial ligation of abdominal aorta].

Partial ligation of the abdominal aorta of rats was adopted to induce left ventricle hypertrophy (LVH). The effects of m-nifedipine (m-Nif) and nifedipine (Nif) on prevention of hypertrophy and the possible mechanism were investigated. The wet weights of the left ventricle (WWLV) of the LVH group were increased compared with those of the sham operated group. After treatment with m-Nif and Nif for 4 wks, the WWLV decreased by 25% +/- 9% and 16% +/- 9%, respectively. The pressure-volume (P-V) curve of the hypertrophied group was markedly elevated, which means that the myocardial compliance was decreased, and the stiffness coefficient of the hypertrophied group was significantly elevated than that of the sham operated group, but the groups treated with m-Nif or Nif were significantly improved. The characteristics of the left ventricular myocardial DHP binding sites were studied. The results showed that the Kd and the Bmax were similar in the m-Nif, Nif and hypertrophied groups, but the total number of the DHP receptors (TNR) of the LVH group was markly increased than that of the sham operated group, but the TNR of the m-Nif and Nif groups were the same as that of the sham operated group. These results suggest that the effects of m-Nif and Nif on preventing cardiac hypertrophy and improving myocardial compliance may be related to their depressing the TNR of DHP.

Animals↗
PubMed1995

DNA- and chromatin-condensing properties of rat testes H1a and H1t compared to those of rat liver H1bdec; H1t is a poor condenser of chromatin.

Histones H1a and H1t are two major linker histone variants present at the pachytene interval of mammalian spermatogenesis. The DNA- and chromatin-condensing properties of these two variants isolated from rat testes were studied and compared with those from rat liver. For this purpose, the histone H1 subtypes were purified from the respective tissues using both acid and salt extraction procedures. Circular dichroism studies revealed that acid exposure during isolation affects the alpha-helical structure of both the globular domain (in the presence of 1 M NaCl) and the C-terminal lambda-tail (in the presence of 60% trifluoroethanol). The condensation of rat oligonucleosomal DNA, as measured by circular dichroism spectroscopy, by the salt-extracted histone H1 was at least 10 times more efficient than condensation by the acid-extracted histone H1. A site size of 16-20 base pairs was calculated for the salt-extracted histone H1. Among the different histone H1 subtypes, somatic histone H1bdec had the highest DNA-condensing property, followed by histone H1a and histone H1t. All the salt-extracted histones condensed rat oligonucleosomal DNA more efficiently than linear pBR-322 DNA. Histones H1bdec and H1a condensed histone H1-depleted chromatin, prepared from rat liver nuclei, with relatively equal efficiency. On the other hand, there was no condensation of histone H1-depleted chromatin with the testes specific histone H1t. A comparison of the amino acid sequences of histone H1d (rat) and histone H1t (rat) revealed several interesting differences in the occurrence of DNA-binding motifs at the C-terminus. A striking observation is the presence of a direct repeat of an octapeptide motif K(A)T(S)PKKA(S)K(T)K(A) in histone H1d that is absent in histone H1t.

Amino Acid Sequence↗
PubMed1995

Effects of tetrandrine on left ventricle hypertrophy in deoxycorticosterone acetate-salt hypertensive rats.

The effect of regression of left ventricular hypertrophy was studied in deoxycorticosterone-acetate-salt hypertensive rats (DOCA-salt hypertensive rats) treated with tetrandrine. Treatment with tetrandrine (by gastric intubation, 50 mg/kg per day for 9 weeks) lowered systolic blood pressure, left ventricular weight, Ca2+ of mitochondria, and markedly decreased the density (Bmax) and total number of dihydropyridine binding sites in hypertrophic left ventricle (P < 0.001). There was no difference between groups in dissociation constant (Kd) values of dihydropyridine binding sites. These facts indicate that tetrandrine decreased cardiac mass in DOCA-salt hypertensive rats through mechanisms that may be associated with the density and the total number of dihydropyridine binding sites, Ca2+ and blood pressure control.

Alkaloids↗
PubMed1995

DNA condensation by the rat spermatidal protein TP2 shows GC-rich sequence preference and is zinc dependent.

Transition protein-2 (TP2), isolated from rat testes, was recently shown to be a zinc metalloprotein. We have now carried out a detailed analysis of the DNA condensing properties of TP2 with various polynucleotides using circular dichroism spectroscopy. The condensation of the alternating copolymers by TP2 (incubated with 10 microM ZnSO4), namely, poly(dG-dC).poly(dG-dC) and poly(dA-dT).poly(dA-dT), was severalfold higher than condensation of either of the homoduplexes poly(dG).poly-(dC) and poly(dA).poly(dT) or rat oligonucleosomal DNA. Between the two alternating copolymers, poly(dG-dC).poly(dG-dC) was condensed 3.2-fold more effectively than poly(dA-dT).poly(dA-dT). Preincubation of TP2 with 5 mM EDTA significantly reduced its DNA-condensing property. Interestingly, condensation of the alternating copolymer poly(dI-dC).poly(dI-dC) by TP2 was much less as compared to that of poly(dG-dC).poly(dG-dC). The V8 protease-derived N-terminal fragment (88 aa) condensed poly(dA-dT).poly(dA-dT) to a very small extent but did not have any effect on poly(dG-dC).poly-(dG-dC). The C-terminal fragment (28 aa) was able to condense poly(dA-dT).poly(dA-dT) more effectively than poly(dG-dC).poly(dG-dC). These results suggest that TP2 in its zinc-coordinated form condenses GC-rich polynucleotides much more effectively than other types of polynucleotides. Neither the N-terminal two-thirds of TP2 which is the zinc-binding domain nor the C-terminal basic domain are as effective as intact TP2 in bringing about condensation of DNA.

Amino Acid Sequence↗
PubMed1995

[Effects of neferine and its combination with taurine on platelet aggregation and experimental thrombosis in rats].

The effects of neferine (Nef), taurine (Tau) and Nef + Tau on platelet aggregation and generation of thrombosis were investigated in rats. Using turbidimetry Nef and Tau were found to inhibit platelet aggregation induced by adenosine diphosphate (ADP), collagen or thrombin. Both drugs reduced the wet weight of experimental thrombosis. But the drugs showed no obvious effect on fibrinogen content and euglobulin lysis time. Thromboxane A2 (TXA2) production induced by ADP and prostacyclin (PGI2) were studied by enzyme immunoassay in rats. TXA2 generation in platelet rich plasma from rats treated with Nef and Nef + Tau obviously decreased. While the plasma PGI2 was not affected. Nef + Tau iv in 30 min significantly decreased the level of total cholesterin in serum. The results suggest that Nef has inhibitory effect on platelet aggregation and thrombosis formation. The combination of both drugs was found to be more potent than either one alone. The mechanism may be related to its reduction of TXA2 formation.

6-Ketoprostaglandin F1 alpha↗
PubMed1995

Myocardial toxicity of cyclosporin A: inhibition of calcium ATPase and nitric oxide synthase activities and attenuation by fructose-1,6-diphosphate in vitro.

Use of cyclosporin A (CsA) in transplantation medicine has been shown to cause a number of toxic cellular side effects, which has prompted a search for formulations that afford protection from these undesirable sequelae. Previously we demonstrated that fructose-1,6-diphosphate (FDP) can reverse a variety of toxic cellular effects that arise upon use of various chemical agents. The present studies were undertaken to study the effects of CsA on rat myocardial Ca2+, calmodulin (Cam)-dependent enzymes such as Ca2+ ATPase and nitric oxide synthase (NOS) and the role of FDP in attenuating these changes in vitro. Rat ventricular sarcoplasmic Ca2+ ATPase was studied by measuring the inorganic phosphorous liberated on ATP hydrolysis and rat heart 100,000 g fraction NOS activity by monitoring the formation of [3H]-citrulline in the presence of 10-1000 microM CsA and 1000 microM CsA + 1000 microns FDP in vitro. CsA in all concentrations significantly (P < 0.001) inhibited both Ca2+ ATPase and NOS activities of rat myocardium and FDP at 1000 microM concentration completely reversed the 1000 microM CsA-inhibited Ca2+ ATPase and cNOS activities of rat myocardium. These data indicate that CsA may inhibit Ca2+ ATPase and NOS activities in the rat myocardium through interference with its Ca2+/Cam-mediated events and thus may cause myocardial toxicity. FDP may reverse these changes.

Animals↗
PubMed1995

[Effects of calcium antagonists on withdrawal of beta-receptor blockers in rats during left ventricular hypertrophy].

The hemodynamic changes of metoprolol (Met, 50 mg.kg-1.d-1, po, 3 wk) withdrawal for 1 day and the effects of nifedipine (Nif) and m-nifedipine (m-Nif) on these changes were observed in pressure overload hypertrophy in rats by abdominal aortic constriction for 4 wk. Both Nif and m-Nif (10 mg.kg-1.d-1, respectively, po, 3 wk) significantly attenuated the increase of MAP (from 14.3 +/- 2.3 to 12.9 +/- 2.3 and 11.3 +/- 2.4 kPa, respectively, n = 6-7, P < 0.05) and decrease the abnormal development of systolic function of left ventricle after Met withdrawal. Radioreceptor assay indicates that Nif and m-Nif can prevent the up-regulation of myocardium beta-receptors in left ventricular hypertrophy and large dose of Met exposure for a long time. These results suggest that calcium antagonists administered with beta-blockers can prevent beta-receptor blocker withdrawal syndrome.

Animals↗
PubMed1995

[Effects of m-nifedipine on dihydropyridine binding sites in the cell membranes of kidney and lung from left ventricular hypertrophied elderly rats].

Effects of m-nifedipine (m-Nif) on the affinity and density of dihydropyridine (DHP) binding sites in the cell membranes of kidney and lung were investigated using the LVH (left ventricular hypertrophy) induced by Goldblatt (2k-1c) renovascular hypertension in elderly rats. m-Nif markedly reduced blood pressure, left ventricular weight, and decreased the density (Bmax) of DHP binding sites in the cell membranes of kidney and lung from 699 +/- 112, 759 +/- 35 fmol.mg-1 protein to 482 +/- 29, 381 +/- 33 fmol.mg-1 protein. No difference was observed between groups in dissociation constant (KD) values of DHP binding sites. The results suggest that m-Nif could markedly decrease DHP binding sites in the membranes of kidney and lung from cardiac hypertrophied elderly rats.

Animals↗
PubMed1995

[Effects of m-nifedipine on left ventricular diastolic function and Ca2+ content of myocardial and cerebral mitochondria and artery tissues in left ventricular hypertrophied rats].

Left ventricular hypertrophy (LVH) was induced by renal hypertension in rats. m-Nifedipine (m-Nif, ig 20 mg.kg-1.d-1 for 9 wk) decreased LV weight in the renovascular hypertensive rats (P < 0.01). The LV compliance in LVH group was significantly decreased compared with that in sham- operated group. The LV stiffness constant, Ca2+ content in left ventricular myocardial and cerebral mitochondria, aorta, and tail artery were markedly raised. m-Nif could markedly reduce the LV stiffness constant, improve the LV compliance, and decrease the Ca2+ content of left ventricular myocardial mitochondria and tissues of artery from LVH rats. These effects of m-Nif were similar to those of nifedipine at the same dosage.

Animals↗
PubMed1995

[Effect of angiotensin and taurine on arrhythmia in cultured neonatal rat hypertrophic heart myocytes].

Angiotensin (Ang) II (1, 10, 100 and 1000 nmol.L-1) was found to increase spontaneous contractile frequency dose-dependently in neonatal rat cardiac myocytes cultured for 3 d. After exposure to Ang II (100 nmol.L-1) for 7 d, neonatal rat heart cells became hypertrophy with increased frequency, elevated APA, prolonged ADP50 and ADP90, and shortened SCL. Addition of ouabian (Oua) 50 nmol.L-1 to the hypertrophic myocytes caused more frequent arrhythmia. Taurine (20 mmol.L-1) was shown to inhibit these changes induced by Ang II. These results suggest that Ang II can increase autorhythmicity as well as sensibility to Oua in cultured cardiac myocytes. These effects might be related to the promotion of Ca2+ influx.

Action Potentials↗
PubMed1995

[Effects of tetrandrine on cardiac hemodynamics of hypertrophied left ventricle from deoxycorticosterone-salt hypertensive rats].

Effects of tetrandrine (Tet) on cardiac mass and hemodynamic parameters were studied in deoxycorticosterone-salt (DOCA-salt) hypertensive rats. Treatment with Tet (50 mg.kg-1, qd x 9 wk) markedly lowered systolic blood pressure and left ventricular (LV) weight. Study on isolated working heart demonstrated that the Tet group compared with the LVH group, AP, LVSP, +/- dp/dtmax, LVDP, coronary blood flow and cardiac output were increased while LVEDP and T were decreased. Studies on LV pressure-volume relation showed that Tet can markedly improve the LV compliance and the LV stiffness constant of LVH rat. These findings suggest that the regression of LVH in DOCA-salt hypertensive rats with Tet is associated with improvement of the contraction, relaxation and pump function, especially relaxation function and hemodynamics.

Alkaloids↗
PubMed1995

In vitro inhibition of rat heart sarcoplasmic reticular membrane ATPase activities by amphotericin B and their reversal by fructose-1,6-diphosphate.

The effect of amphotericin B on rat heart sarcoplasmic reticular membrane Na(+)-K+ and Ca2+ ATPase activities in vitro was investigated. Amphotericin B in selected concentrations of 100-1000 ng significantly inhibited the sarcoplasmic reticular membrane ATPase activities studied. Fructose-1,6-diphosphate (1000 microM concentration) completely reversed the inhibition of Ca2+ ATPase activity in particular, but failed to reverse that of Na+(-)K+ATPase activities at 1000 microM concentration. Fructose-1,6-diphosphate may afford some protection against 1000 ng amphotericin B-induced myocardial toxicity. These damages may vary depending upon the dose of amphotericin B used in experimental studies.

Adenosine Triphosphatases↗
PubMed1995

[Effects of praeruptorin C on spontaneous contraction and action potential in cultured myocardial cells of neonatal rats].

Using a circuit TV system and method of intracellular standard microelectrode, the effects of praeruptorin C on spontaneous contractile behavior and action potential were observed in cultured myocardial cells of neonatal rats. There was a decline in both the contractile frequency and velocity of cell edge motion after exposure to Pra-C for 5 minutes. Pra-C (10, 30 and 100 mumol.L-1) was shown to inhibit contraction velocity by 24%, 43% and 51%, respectively in a concentration dependent manner. Pra-C (30 and 100 mumol.L-1) inhibited the contractile frequency by 13% and 19%, respectively. Nifedipine 3 mumol.L-1 shortened APD50 and APD90 by 14% and 17% but verapamil at the same concentration inhibited APA by 27%, shortened APD50 by 8% and prolonged APD90 and SCL by 10% and 43%, respectively. Pra-C 10, 30 and 100 mumol.L-1 shortened the APD50 by 7%, 14% and 18%, respectively. Pra-C 30 mumol.L-1 inhibited APA and prolonged SCL. The results suggest that the effects of Pra-C on contractile behavior and action potential were related to its Ca2+ channel blockade.

Action Potentials↗
PubMed1995

[Effects of taurine and enalapril on blood pressure, platelet aggregation and the regression of left ventricular hypertrophy in two-kidney-one-clip renovascular hypertensive rats].

In two-kidney-one-clip (2k-1c) renovascular hypertensive rats, the blood pressure, left ventricular weight/body weight (LVW/BW) ratio and blood platelet aggregation were increased significantly. Enalapril (Ena) 6 mg . kg-1 . d-1 ig 9 wk and Taurine 30 mg . kg-1 . d-1 ig 9 wk can not only decrease the high blood pressure, LVW/BW ratio, but also the blood platelet aggregation induced by ADP or thrombin, though still different from that of the normal group. When the 2k-1c renovascular hypertensive rats were treated with both Ena and Tau, the blood pressure and blood platelet aggregation were decreased to the same as that of the normal group, and the LVW/BW ratio was also lowered markedly, though still higher than that of the normal group. These results show that both Ena and Tau can reverse the left ventricular hypertrophy, decrease the blood pressure and suppress the blood platelet aggregation in 2k-1c renovascular hypertensive rats. When treated with both drugs, the effects can be improved. It suggests that the two drugs can enhance the effects when used together, and that they may be two good agents for treatment of hypertension.

Animals↗
PubMed1994

Characterization of the zinc-metalloprotein nature of rat spermatidal protein TP2.

Spermatidal transition protein, TP2, was purified from rat testes by Hg-affinity chromatography. The present study reports the details of the zinc-metalloprotein nature of TP2 by employing the 65 Zn-blotting technique. Chemical modification of cysteine by iodoacetic acid, and histidine by diethylpyrocarbonate, resulted in a near complete inhibition of 65Zn-binding to TP2. The 65Zinc-binding was localized to the V8 protease-derived N-terminal two-third polypeptide fragment. Circular dichroism spectroscopy studies of TP2 (zinc pre-incubated) and its V8 protease-derived polypeptide fragments revealed that the N-terminal fragment has a Type I-beta-turn spectrum, while the C-terminal fragment has a small but significant alpha-helical structure. EDTA altered the circular dichroism spectrum of TP2 and the N-terminal fragment (zinc binding domain) but not that of the C-terminal fragment.

Amino Acid Sequence↗
PubMed1994

Structure of the human MSH2 locus and analysis of two Muir-Torre kindreds for msh2 mutations.

Hereditary nonpolyposis colorectal carcinoma (HNPCC) is a major cancer susceptibility syndrome known to be caused by inheritance of mutations in genes such as hMSH2 and hMLH1, which encode components of a DNA mismatch repair system. The MSH2 genomic locus has been cloned and shown to cover approximately 73 kb of genomic DNA and to contain 16 exons. The sequence of all the intron-exon junctions has been determined and used to develop methods for analyzing each MSH2 exon for mutations. These methods have been used to analyze two large HNPCC kindreds exhibiting features of the Muir-Torre syndrome and demonstrate that cancer susceptibility is due to the inheritance of a frameshift mutation in the MSH2 gene in one family and a nonsense mutation in the MSH2 gene in the other family.

Amino Acid Sequence↗