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Biomedical subjects

F Nakamura

Publications and source records attributed to F Nakamura.

At least 181 records · Page 10Linked to original sources
PubMed1992

Role of cardiac angiotensin II in isoproterenol-induced left ventricular hypertrophy.

Angiotensin II (Ang II) has been shown to induce proliferation of cardiac myocytes. To examine the role of Ang II in left ventricular (LV) hypertrophy, isoproterenol was infused subcutaneously into 9-week-old male Wistar rats at 4.2 mg/kg/day for 7 days. Infusion of isoproterenol increased LV weight and Ang II concentrations in plasma and in LV tissue. In anephric rats, LV weight and tissue Ang II were increased similarly, but plasma Ang II was not changed by isoproterenol. Concomitant oral administration of trandolapril and isoproterenol prevented increases in both LV Ang II and LV weight. Treatment with hydralazine decreased blood pressure in a similar way as trandolapril but did not affect either LV weight or LV Ang II. Plasma Ang II was not decreased by either trandolapril or hydralazine when administered in combination with isoproterenol. These results suggest that cardiac tissue Ang II regulates myocyte growth in isoproterenol-induced LV hypertrophy, and the reduction of Ang II partly explains the prevention of cardiac hypertrophy by the converting enzyme inhibitor.

Angiotensin II↗
PubMed1992

Cardiac sarcoplasmic reticulum chloride channels regulated by protein kinase A.

In heart cells, several plasma membrane ion channels are targets for phosphorylation. However, it is not known whether sarcoplasmic reticulum (SR) ion channels, which are also essential in the regulation of cardiac function, are regulated by second-messenger systems. Here, we show that a Cl- channel in the cardiac SR membrane is activated by the catalytic subunit of protein kinase A (PKA). Purified cardiac heavy SR vesicles were incorporated into planar lipid bilayers. This channel spontaneously inactivated within a few minutes after the channel was incorporated into the bilayer. Mg-ATP (2-5 mM), but not the nonhydrolyzable ATP analogue 5'-adenylylimidodiphosphate, added to the cis solution prevented this spontaneous channel inactivation. After the inactivation process occurred, the catalytic subunit of PKA (with 0.05 mM Mg-ATP) reactivated this channel. These effects of Mg-ATP and PKA on the Cl- channel were prevented by an inhibitor of PKA. Thus, these results suggest that this SR Cl- channel is a novel target of PKA-dependent phosphorylation in cardiac muscle regulation.

Adenosine Triphosphate↗
PubMed1992

[The vasospasmolytic effects of nicorandil, cromakalim and pinacidil on 3,4-diaminopyridine-induced phasic contractions in canine coronary arteries as an experimental vasospasm model].

The spasmolytic mechanisms of nicorandil, a novel antianginal drug, were investigated using 3,4-diaminopyridine (3,4-DAP)-induced phasic contractions of isolated canine coronary arteries in comparison with those of cromakalim and pinacidil. Nicorandil (10(-4) M), cromakalim (10(-6) M) and pinacidil (10(-5) M) suppressed the phasic contractions. Pretreatment with glibenclamide (10(-6) M), a specific blocking agent of ATP-sensitive K+ channel, eliminated the suppression of phasic contractions by these drugs; glibenclamide completely eliminated the suppression by cromakalim, while the eliminations against nicorandil and pinacidil were incomplete. The recoveries of peak tensions were only 56.8% and 76.1% for nicorandil and pinacidil, respectively. Nicorandil and pinacidil may suppress the phasic contractions via K+ channel opening and additional mechanisms. Methylene blue (10(-7)-10(-5) M) alone, a guanylate cyclase inhibitor, had no effect on the suppression of phasic contractions by nicorandil. In the presence of glibenclamide (10(-6) M), however, the pretreatment with methylene blue significantly augmented the recovery of peak tension for nicorandil. These results indicate that K+ channel openers may suppress the phasic contractions induced by 3,4-DAP via ATP-sensitive K+ channels, and that additionally, nicorandil may suppress the phasic contractility through guanylate cyclase stimulation, as a nitrate.

4-Aminopyridine↗
PubMed1992

Regression of hypertension-induced vascular hypertrophy by an ACE inhibitor and calcium antagonist in the spontaneously hypertensive rat.

This study was designed to investigate the effects of antihypertensive drugs on vascular hypertrophy and vascular angiotensin II in vivo in spontaneously hypertensive rats (SHR). Hydralazine (10 mg/kg/day), delapril (angiotensin converting enzyme inhibitor; 20 mg/kg/day), manidipine (calcium channel blocker; 10 mg/kg/day), and vehicle were given by gavage to four groups of SHR between 4 and 5 months of age. The aortic angiotensin II level was measured by highly sensitive radioimmunoassay coupled with high pressure liquid chromatography; aortic morphologic studies were performed. Each drug treatment effectively lowered blood pressure to the same level. However, the aortic wall thickness, medial-intimal areas, and wall to lumen ratio of abdominal aorta decreased significantly (p < 0.05, p < 0.01, p < 0.01, respectively) with delapril and manidipine but not hydralazine. Delapril significantly decreased aortic angiotensin II levels (p < 0.05), whereas manidipine treatment significantly increased them (p < 0.05). The aortic angiotensin II level was not changed by hydralazine. These results show that delapril and manidipine caused regression of hypertension-induced vascular hypertrophy in SHR. The probable mechanism of regression of aortic hypertrophy by delapril was inhibition of vascular angiotensin II formation, but the mechanism for manidipine was unclear.

Angiotensin II↗
PubMed1991

Identification of two novel GTP-binding protein alpha-subunits that lack apparent ADP-ribosylation sites for pertussis toxin.

Molecular cloning of cDNAs encoding alpha-subunits of guanine nucleotide-binding regulatory proteins (G-proteins) has revealed the existence of nine species of alpha-subunits. We have identified two additional G-protein alpha-subunits, which we refer to as GL1 alpha and GL2 alpha, by isolating bovine liver cDNA clones that cross-hybridized at reduced stringency with bovine Gi1 alpha-subunit cDNA. The deduced amino acid sequences of GL1 alpha and GL2 alpha share 83% identity with each other and show 45-55% identity with those of other known G-protein alpha-subunits. Both GL1 alpha and GL2 alpha lack a consensus site for ADP-ribosylation by pertussis toxin. Messenger RNA corresponding to GL2 alpha was detected in all tissues examined, but GL1 alpha mRNA was detected only in liver, lung, and kidney. Antiserum prepared against a synthetic pentadecapeptide corresponding to the deduced carboxyl terminus of GL2 alpha specifically reacted with a 40-kDa protein in mouse liver, brain, lung, heart, kidney, and spleen. The amount of the 40-kDa protein was highest in brain and lung. We suggest that GL1 alpha and GL2 alpha are new members of a subfamily of pertussis toxin-insensitive G-proteins.

Adenosine Diphosphate Ribose↗
PubMed1991

The catalytic subunit of cyclic AMP-dependent protein kinase directly inhibits sodium channel activities in guinea-pig ventricular myocytes.

We investigated the effects of the purified catalytic subunit (C subunit) of the cAMP-dependent protein kinase (A-kinase) on the cardiac Na+ channel currents. Single Na+ channel currents in guinea-pig ventricular myocytes were recorded using the patch clamp technique of the inside-out configuration. Application of C subunit decreased the peak average current and slowed the current decay, effects which were caused by decrease in the open probability of Na+ channels and increase in the first latency, whereas the unitary current amplitude and mean open times were not affected. We conclude that the cardiac Na+ channel is directly modulated by phosphorylation process through A-kinase.

Animals↗
PubMed1991

Silica gel high-performance liquid chromatography for the determination of cross-links in elastin.

A high-performance liquid chromatographic (HPLC) procedure for the determination and preparation of desmosine (DES) and isodesmosine (IDE), the major cross-links of elastin, has been developed. Hydrolysates of elastin are treated with a SEP-PAK silica-gel small column and then separated on a silica-gel normal phase column using n-propanol-water-25% ammonia (9:3:0.06, v/v/v) followed by detection at 275 nm. The quantitative yields of DES and IDE are 7.98 +/- 0.47 and 6.44 +/- 0.51 (mean +/- S.D., n = 10) mg/g dry weight, respectively, in bovine ligamentum nuchae. Preparations of cross-links are carried out by means of a preparative column (240 mm x 10 mm), using the same solvent system.

Amino Acid Sequence↗
PubMed1991

Converting enzyme inhibitors regressed cardiac hypertrophy and reduced tissue angiotensin II in spontaneously hypertensive rats.

To examine the role of the tissue renin-angiotensin system in left ventricular hypertrophy, converting enzyme inhibitors were administered orally to 12-week-old male spontaneously hypertensive rats (SHR) for 4 weeks, and cardiac tissue angiotensin II was measured. Treatment with enalapril (10 mg/kg per day) and trandolapril (1 mg/kg per day) lowered systolic blood pressure, left ventricular weight and left ventricular angiotensin II content. Plasma angiotensin II concentration was increased by the treatment with enalapril whereas trandolapril did not cause any change. There was significantly positive correlation between left ventricular weight and angiotensin II content. Because angiotensin II promotes cell proliferation, these results suggest that cardiac tissue angiotensin II, rather than circulating angiotensin II, may account for the pathophysiology of left ventricular hypertrophy in SHR.

Angiotensin II↗
PubMed1991

Effect of long-term treatment with an angiotensin-converting enzyme inhibitor on the renin-angiotensin system in spontaneously hypertensive rats.

1. To obtain information on regulation of the brain renin-angiotensin system, the effect of long-term administration of angiotensin-converting enzyme (ACE) inhibitor on brain renin and angiotensinogen mRNA was studied. 2. Spirapril (3 mg/kg) was orally administered daily for 8 weeks to spontaneously hypertensive rats (SHR) from 12 weeks after birth. Renin and angiotensinogen mRNA in the brain and kidney were then quantitated by Northern blot analyses with [32P]-labelled rat renin and angiotensinogen cDNA as hybridization probes. Plasma renin activity (PRA), angiotensin II (AII) concentration, plasma ACE activity and brain tissue ACE activity were also measured. 3. Compared with the control group, the Spirapril-treated group had significantly lower blood pressure (P less than 0.01), significantly higher PRA (P less than 0.01), a not significantly different plasma AII concentration, and lower plasma and brain ACE activities (P less than 0.01). Interestingly, the brain renin and angiotensinogen mRNA levels of the two groups were similar, but the renal renin mRNA level was significantly higher in the Spirapril-treated group (P less than 0.01). 4. These results indicate that the mRNA levels of brain renin and angiotensinogen were not affected by chronic ACE inhibition in the circulation and suggest that AII in the brain might not be affected by systemic ACE inhibition.

Actins↗
PubMed1991

Holmium YAG laser coronary angioplasty with multifiber catheters.

Excimer lasers are being extensively used for coronary angioplasty along with multifiber over-the-wire catheters. To determine whether another wavelength could be an alternative, the laser-tissue interaction and the clinical usefulness of an infrared laser were studied. The laser consisted of a Holmium YAG pulsed laser coupled into a multifiber catheter. Experimental data from our laboratory showed that this solid state laser had the ability to cut calcified tissue, to be preferentially absorbed by atheroma, and to ablate tissue even when the catheter tip was positioned at a distance from the target. These results were obtained with only minimal thermal effects. After assessment of the efficacy and safety of this technique, laser angioplasty was performed in 53 consecutive patients with totally occluded (40%) or stenosed (mean percent 94) coronary arteries with a mean length of 6 mm. The primary laser and the procedure success rate were 64% and 94%, respectively. Failures were due to inability to advance the catheter against the lesion or to cross the obstruction. Stand-alone laser therapy could be achieved in only 18% of patients. In previous dilatation failures, laser irradiation allowed for subsequent balloon angioplasty to be successfully performed at a lower inflation pressure than that used in the failed dilatation. Complications included abrupt (during the procedure) and early (within 24 hours) vessel closure in 19% of cases, dissection without hemodynamic consequence in 28% and spasm. Reoccluded arteries could all be recanalized with dilatation.(ABSTRACT TRUNCATED AT 250 WORDS)

Angioplasty, Laser↗
PubMed1991

Percutaneous fiberoptic cardioscopy of the left ventricle.

The feasibility of percutaneous transluminal cardioscopy of the left ventricle was examined in 35 patients with or without various heart diseases. A guiding balloon catheter (7 or 9 French) was introduced through the right femoral artery into the left ventricle. The balloon was inflated, and a fiberscope (1.6 or 4.3 French) was advanced to the distal tip of the catheter. The balloon was then manipulated against the portion of the ventricle targeted for examination, and heparinized saline (10 U/ml) at body temperature was infused through the catheter at 5 ml/sec for 3 to 6 sec. The images were recorded on videotape and 16 mm cinefilm. In 4 patients without demonstrable heart disease, the endocardial surface of the left ventricle was brown and the trabeculae became prominent during systole. The chordae connected to the mitral leaflets were white. In 3 of 5 patients with dilated cardiomyopathy, the endocardium was light yellow with thin trabeculae which barely contracted during systole. The endocardium was red or reddish-brown in 3 patients with acute myocarditis. In patients with rheumatic mitral stenosis white patches were scattered on the endocardial surface. In 7 of 8 patients the akinetic or dyskinetic segments representing prior infarctions were white. No complications other than transient ventricular arrhythmias were noted. We conclude that percutaneous fiberscopic imaging with a guiding balloon catheter is feasible and safe, and yields highly detailed images of the endocardium.

Acute Disease↗
PubMed1991

Substrain comparison of genetically hypertensive rats using DNA fingerprinting, and genetic analysis of blood pressure in the inbred rats.

Using DNA fingerprinting, genetic heterogeneity or homogeneity was studied between substrains of spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats maintained in Japan. Using human myoglobin minisatellite 33.15 as a probe, we did not detect any inter- or intra-substrain genetic heterogeneities in HinfI digests of SHR or WKY rat DNA. However, analysis of Sau3AI digests of rat DNA using mouse C-6 gene as a probe revealed intra-substrain heterogeneity of 1-2 DNA bands in one of the WKY rat substrains. In the other substrains of SHR and WKY rats, there existed no intra-substrain heterogeneities, but several inter-substrain heterogeneities were observed in both SHR and WKY rats. In another experiment using the inbred substrains of SHR and WKY rats which have been confirmed as genetically homogeneous, we produced F1 and F2 rats, and biometrically analyzed their systolic blood pressure. The results suggested that there may be 1-4 dominant antihypertensinogenic genes with high heritability of 0.6-0.7.

Animals↗
PubMed1991

Angiographic morphology of the posterior communicating artery and basilar in patients with ICA-PComA aneurysm.

The relationships between the angiographic morphology of the posterior communicating artery (PComA) and the basilar artery (BA) and saccular aneurysms at the internal carotid artery (ICA)-PComA junction were evaluated in 23 patients with ICA-PComA aneurysm and 46 controls. No significant differences were found in the height of the basilar top, the dislocation and inner diameter of the BA, and the distance between the basilar top and the ICA-PComA junction. However, the angle between the PComA and C2 portion of the ICA was larger and the PComA straighter in ICA-PComA aneurysm patients. Tension in the PComA and mechanical damage to the divergent angle of the PComA are probably important factors in the development of ICA-PComA aneurysms.

Basilar Artery↗