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Biomedical subjects

I Yamaguchi

Publications and source records attributed to I Yamaguchi.

At least 253 records · Page 14Linked to original sources
PubMed1987

Inflammatory responses in cuff-induced atherosclerosis in rabbits.

Cuff-treatment of the rabbit carotid artery produced a diffuse intimal thickening which resembled early lesions of atherosclerosis. A limited amount of focal endothelial damage occurred first (0.5 h), leukocytes infiltrated the subendothelium and extensive endothelial denudation occurred at 24 h. At 3 days, the regenerating endothelium covered the denuded area, and the media was edematous. At 7 days proliferation of intimal cells became visible. Maximum intimal thickening occurred at 3 weeks. Daily injection of dexamethasone (0.01-10 mg/kg i.m.) and ticlopidine (1-100 mg/kg i.m.) dose-dependently attenuated the intimal thickening. Indomethacin had little effect. Inflammatory exudate from zymosan-activated air pouch induced chemotaxis of rat smooth muscle cells (SMC) in vitro. Similar chemotactic activity was observed with leukotriene B4 (LTB4) but not with the other lipoxygenase products tested. The exudate contained reasonable amounts of LTB4, which would account for its chemotactic activity. Dexamethasone inhibited the chemotaxis by the exudate and proliferation of SMC. These results are discussed in relation to the mechanism of atherogenesis. It is concluded that leukocytes play a major role in cuff-induced intimal thickening, and that their products cause endothelial denudation and SMC chemotaxis. Involvement of platelet aggregation in atherogenesis is also suggested.

Animals↗
PubMed1987

Antiatherogenic activity of FR34235 (Nilvadipine), a new potent calcium antagonist. Effect on cuff-induced intimal thickening of rabbit carotid artery.

The antiatherogenic activity of FR34235 (Nilvadipine), a calcium antagonist, was examined in rabbits with carotid arteries sheathed with polyethylene cuffs, and compared with that of nifedipine, verapamil and diltiazem. The drugs were given intramuscularly in daily doses of 0.01-10 mg/kg for 3 weeks, starting on the day of cuff-placement. FR34235 dose-dependently inhibited the cuff-induced intimal thickening, and was more potent than the other calcium antagonists, whose order of potency was nifedipine, diltiazem and verapamil. In an in vitro experiment on inhibition of migration of rat aortic smooth muscle cells, using zymosan-activated air pouch exudate as a chemoattractant in modified Boyden chambers, FR34235 was also the most potent among the calcium antagonists tested. The IC50 values were 3.3 X 10(-11) M for FR34235, 1.7 X 10(-10) M for nifedipine, 6.0 X 10(-9) M for verapamil and 2.4 X 10(-7) M for diltiazem. Effects of these drugs on proliferation of rat aortic smooth muscle cells and rabbit platelet aggregation were also examined in vitro. At concentrations less than 10(-5) M, none of the drugs inhibited proliferation of the smooth muscle cells, and only verapamil inhibited collagen-induced platelet aggregation (IC50 = 9.0 X 10(-7) M). It is suggested that FR34235 should be useful for preventing and treating atherosclerosis. Inhibition of smooth muscle cell migration is thought to be its mechanism of antiatherogenic activity.

Animals↗
PubMed1987

Pharmacological effects of nicergoline and its metabolites, decomposition products and impurities in animals.

The main pharmacological effects and acute toxicity of nicergoline (NCG, ester type), its 5 metabolites [1-DN (ester type), 1-MMDL, 1-OHMMDL, MDL (ergoline-alcohol type) and 5-BNA (bromonicotinic acid)], 2 decomposition products (1-MMDL and 5-BNA) and 2 impurities [1-DN and 5-CN (ester type)] were studied in animals. In mice, the acute intraperitoneal toxicity of 1-MMDL, 1-OHMMDL and 5-CN was similar to that of NCG (LD50 197.6 mg/kg). The toxicity of 1-DN, MDL and 5-BNA was approximately 2-fold, 2- fold and one half of NCG, respectively. These substances caused no delayed death. In protective effects against KCN- and adrenaline-induced death in mice when given i.p., 1-DN and 1-MMDL were less potent than NCG, and 1-CN was similar in potency to NCG. In competitive inhibitory effects on phenylephrine-induced contraction of isolated guinea pig vas deferens, 1-DN was less potent, 1-MMDL was much less potent and 5-CN was more potent than NCG. In an inhibitory effect on collagen-induced platelet aggregation in vitro using rat platelet-rich plasma, 1-DN and 5-CN were similar in activity to NCG and 1-MMDL was less active than NCG. On the other hand, 1-OHMMDL, MDL and 5-BNA were inactive in these experiments. In experiments on gross behavior, motor function and barbital anesthesia using mice, when given i.p., 5-CN as well as NCG moderately induced depressive effects on the central nervous systems. 1-DN and 1-MMDL were less potent in the effects than NCG. In anesthetized rats, when given i.v., 1-DN and 5-CN dose-dependently caused lowering effects on blood pressure similar to NCG. 1-MMDL and 1-OHMMDL were less potent than NCG in the lowering effect. 1-DN and 5-CN moderately decreased the contractile force in the isolated guinea pig heart when given i.a. 5-CN alone decreased urine volume in rats when given i.p. and all the substances had no effect on the intestinal transit ability in mice when given i.p. These results suggest that the pharmacological effects of NCG are due to NCG per se and in part to its metabolites. As regards structure-activity relationships, NCG, 1-DN and 5-CN with an ester linkage were found to be more potent in pharmacological activities than ergoline-alcohol compounds.(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1986

Effects of propranolol on myocardial damage resulting from coronary artery occlusion followed by reperfusion.

To evaluate the effects of propranolol on myocardial metabolism after coronary reperfusion, serial measurements of myocardial creatine kinase (CK) and calcium (Ca) contents and CK and lactic acid (LA) concentrations in coronary sinus blood were carried out in 33 open-chest dogs. The left anterior descending coronary artery was occluded for 60 minutes and was then reopened. Twelve of the dogs were given propranolol before occlusion. Reperfusion for 30 minutes in dogs with and without propranolol pretreatment resulted in reduced myocardial CK in the ischemic region and rapidly elevated plasma CK and LA. However, when compared with the control group, the propranolol-treated group showed smaller changes in myocardial CK and plasma LA. Myocardial Ca in the ischemic region was significantly higher than that in the nonischemic region in the control group, but not in the propranolol-treated group. It was concluded that propranolol was protective against myocardial damage resulting from coronary occlusion followed by reperfusion.

Animals↗
PubMed1986

Intersubject variability in cardiac output-O2 uptake relation of men during exercise.

Intersubject variability in the relation between cardiac output (Q) and O2 uptake (VO2) was examined during supine cycling up to the maximum level in 40 normal untrained men age 27 +/- 4 (SD) yr. In individual subjects, Q increased linearly against VO2 in the submaximum exercise range. The SD of Q on VO2 was so small (0.47 +/- 0.25 l/min) that Q could be given by a linear function of VO2 as Q = K(VO2 - VO2 r) + Qr, where K, VO2 r, and Qr are the slope of the regression line, the resting VO2, and resting Q, respectively. K varied widely among the subjects studied, ranging from 5.5 to 10.3 and was independent of both physical characteristics and Qr, which ranged from 3.7 to 8.3 l/min. However, K correlated significantly with changes in heart rate, stroke volume, mean arterial pressure, and systemic vascular conductance. From these results, we concluded that the intersubject variability in the Q-VO2 relation was caused independently by individual variations in resting hemodynamics and in cardiovascular response to exercise.

Adult↗
PubMed1986

Effects of diltiazem on renal blood flow and renal function during angiotensin II infusion in anesthetized dogs.

Effects of diltiazem on renal blood flow and renal function were studied under angiotensin II-loaded condition in anesthetized dogs. Intravenous infusion of angiotensin II at a rate of 0.25 microgram/kg/min produced an increase in blood pressure by 30 to 40 mmHg and a decrease in renal blood flow by 30 to 40%, resulting in a 100% increase in renal vascular resistance. Under this condition, diltiazem exhibited a dose related increase in renal blood flow not only by intrarenal administration (1-30 micrograms/kg) but also by intravenous administration (10-200 micrograms/kg). The effect was greatly augmented, compared to that observed in a control angiotensin II-unloaded condition. Under angiotensin II-loaded condition, glomerular filtration rate and para-amino-hippuric acid clearance, as well as renal blood flow, were markedly reduced, the levels of which were recovered by intrarenal administration of diltiazem (10 micrograms/kg/min) accompanied by marked natriuresis. The natriuretic effect of diltiazem was also observed by intravenous administration (100 micrograms/kg). It is suggested that the improving effects of diltiazem on renal hemodynamics and renal function, under angiotensin II-loaded condition, are mainly due to its inhibitory action on angiotensin II-evoked renal vasoconstriction, resulting from its calcium antagonistic action.

Angiotensin II↗
PubMed1985

Calcium entry blockers: antihypertensive and natriuretic effects in experimental animals.

Hypotensive and natriuretic effects of calcium entry blockers were studied in spontaneously hypertensive rats (SHRs) and normotensive Wistar Kyoto rats (WKYs). In SHRs, the hypotensive action of diltiazem was enhanced, while that of hydralazine was not different from its action in WKYs. Diltiazem, unlike hydralazine and nifedipine, did not cause reflex tachycardia in rats. Diltiazem and nifedipine caused an increase in urine volume and sodium excretion. The natriuretic potency of diltiazem was the same in both SHRs and WKYs and was not affected by pretreatment with indomethacin. Diltiazem increased plasma renin activity but had no influence on plasma aldosterone concentration. Hydralazine increased both plasma renin activity and plasma aldosterone concentration and decreased sodium excretion. In anesthetized dogs, diltiazem increased sodium excretion, glomerular filtration rate and renal blood flow. Diltiazem may have a direct effect on tubular sodium reabsorption. This assumption was supported by a study with short-circuit current of the isolated bullfrog bladder. It is likely that diltiazem's effect of increasing urine volume and sodium excretion is due mainly to changes in renal hemodynamics and partly to direct action on renal tubules. Diltiazem opposed angiotensin II-induced responses, such as renal vasoconstriction and reduction of glomerular filtration rate. Under this condition, a marked natriuretic effect was observed with both intravenous and intraarterial administration of diltiazem. The ability to increase urinary excretion of sodium is a desirable characteristic for an antihypertensive agent. Calcium entry blockers have this ability and are therefore able to act without causing sodium and water retention.

Angiotensin II↗