Biomedical subjects

H Mikami

Publications and source records attributed to H Mikami.

316 records · Page 18Linked to original sources

PubMedDate not supplied

Effect of cromakalim (BRL 34915) on hemodynamic and electrocardiographic changes induced by endothelin in dogs.

We evaluated whether cromakalim (BRL 34915), a vasorelaxant agent which acts by opening potassium channels, could affect the systemic effects of endothelin, a newly discovered vasoconstrictive peptide. Intravenous administration of endothelin alone (400 pmol/kg) to anesthetized dogs produced blood pressure elevation, which was associated with an increase in cardiac output in the early phase, and was associated with an increase in total peripheral resistance in the late phase. Electrocardiogram showed significant ST-elevation in II, III, and aVF, and ST-depression in aVR and aVL. The same dose of endothelin given to dogs pretreated with cromakalim did not induce these hemodynamic and electrocardiographic changes. Thus, cromakalim, a potassium activator, inhibited the hemodynamic and electrocardiographic actions of endothelin, suggesting that hyperpolarization due to potassium channel activation inhibited the voltage-dependent calcium channel, which is thought to be a major mechanism for the pressor action of endothelin.

Animals↗

PubMedDate not supplied

Effect of cilazapril therapy on glucose and lipid metabolism in patients with hypertension.

The effects of long-term monotherapy with cilazapril, an angiotensin-converting enzyme inhibitor, on blood pressure, glucose tolerance, and serum lipid profiles were prospectively investigated in 66 patients with hypertension: 23 with normal glucose tolerance and 43 with glucose intolerance (including 9 patients with non-insulin-dependent diabetes mellitus). The levels of plasma glucose, serum insulin, serum lipids, glycated hemoglobin A(lc) (Hb A(lc)), and fructosamine were determined before and during long-term (mean +/- SD, 26.2 +/- 1.2 weeks) therapy with cilazapril. A 75-g oral glucose tolerance test was performed before and during treatment. Significant reductions in both systolic and diastolic blood pressures in both patient groups were maintained during the study. Neither fasting nor post-glucose load venous plasma glucose levels were altered in either group of patients, and no patient with normal glucose tolerance developed diabetes mellitus during the study. There was no significant change in the insulinogenic index (delta serum insulin/delta venous plasma glucose at 30 minutes post-glucose load) in either group, and glucose intolerance was slightly improved with significant reductions (P < 0.01) in Hb A(lc) and fructosamine in the patient group with impaired glucose tolerance. Serum total cholesterol (TC), low-density lipoprotein cholesterol, and triglyceride levels were significantly (P < 0.01) decreased and high-density lipoprotein cholesterol levels increased in patients with hypercholesterolemia (TC levels > or = 5.69 mmol/L). These results suggest that long-term cilazapril therapy may improve glucose and lipid metabolism in hypertensive patients with impaired glucose tolerance. Cilazapril also appears to be useful as an antihypertensive agent for hypertensive patients with either impaired glucose tolerance or hypercholesterolemia.

Angiotensin-Converting Enzyme Inhibitors↗

PubMedDate not supplied

Maternal inheritance of mitochondrial cytochrome c oxidase activity in mice.

The RR mouse strain has unique restriction fragment patterns of mitochondrial DNA and shows lower activity of cytochrome c oxidase in fresh liver mitochondria than do C57BL/6 and BALB/c mice after nine weeks of age. In reciprocal F1 crosses between RR and the other two strains, the activity of crosses from RR mothers was lower than that in reciprocal crosses, although both F1 crosses had values intermediate between those of the parental strains. Cross-nursing tests demonstrated that strain differences probably are determined before or immediately after birth. Successive backcrossing was performed in order to transfer mitochondrial DNA from one strain to the nuclear background of another strain, and after eight and 10 generations, the cytochrome c oxidase activities of the backcross lines were compared with those of the maternal and paternal strains. The activity of the backcross line that started with C57BL/6 or BALB/c females and was successively backcrossed to RR males was still higher than that of RR. Similarly, the line that started with RR females and was backcrossed to C57BL/6 or BALB/c males showed lower activity than that of the paternal strain. These observations suggest that part of the strain difference of cytochrome c oxidase activity is transmitted by mitochondrial DNA, although our evidence does not exclude the possible involvement of other maternally transmitted components.

Aging↗

PubMedDate not supplied

Immunoreactivity to M2 proteins in antimitochondrial antibody-negative patients with primary biliary cirrhosis.

Although antimitochondrial auto-antibodies are characteristically present in the serum of patients with primary biliary cirrhosis (PBC), there is a discrepancy between the positivity for antimitochondrial antibody (AMA) and that for anti-M2 auto-antibody. In an attempt to explain the discrepancy, this study investigates the relationship between the AMA titre, determined by indirect immunofluorescence, and immunoreactivity to four inner mitochondrial membrane proteins (M2 proteins) with molecular weights of 70, 50, 47, and 40 kDa in 129 patients with PBC. Antimitochondrial antibody positivity was identified in 114 (88%) of 129 patients with clinically and histologically confirmed PBC. There were no significant differences between the AMA-negative and AMA-positive groups in clinical characteristics or histologically determined disease stage. Immunoblot analysis showed that all patients had anti-M2 auto-antibodies to one or more of the four M2 proteins. Nine (60%) of the 15 AMA-negative patients had antibodies to only one M2 protein (either 70 or 47 kDa). In contrast, 34 (53%) of the 64 patients with high AMA titres (> or = 1:320) had antibodies to all four M2 proteins. There was a significant rank correlation between the AMA titre and the number of antibodies to M2 proteins (P < 0.01). These findings indicate that the AMA titre is not influenced by the immunogenicity of M2 proteins but by the number of M2 proteins that elicit an antibody response and that decreased immunoreactivity to M2 proteins may induce AMA negativity in PBC serum samples.

Adult↗

PubMedDate not supplied

Cerebrospinal fluid angiotensin II immunoreactivity is not derived from the plasma.

To elucidate whether the presence of angiotensin II immunoreactivity (ANG II-ir) in the cerebrospinal fluid (CSF) of the dog is in part due to passage of the peptide across the CSF-blood-brain barrier, [Ile5] angiotensin II (ANG II) was infused intravenously for 7 days in conscious, trained dogs at a rate of 10 micrograms/kg/day. Mean arterial pressure (MAP) and heart rate were monitored each day, and samples of arterial blood and CSF (with a catheter secured into the cisterna magna) were drawn at regular intervals for determination of catecholamine levels, ANG II-ir, and electrolyte levels. Within 2 days after ANG II infusion, MAP stabilized at 35 +/- 1 mm Hg (mean +/- SE, p less than 0.001) above control values. The hypertension was associated with bradycardia, suppressed plasma renin activity, and a fall in both plasma and CSF Na+ concentrations. These changes coincided with a considerable and sustained decrease in the levels of plasma and CSF norepinephrine. On the other hand, levels of epinephrine and K+ in the two compartments remained unchanged. Although concentration of ANG II-ir in plasma was augmented markedly (368% above control values, p less than 0.001), ANG II-ir in the CSF remained within the low values measured in the control period.(ABSTRACT TRUNCATED AT 250 WORDS)

Angiotensin II↗

PubMedDate not supplied

Effect of aging on the renin angiotensin system in patients with renovascular hypertension.

The effect of aging on the renin angiotensin system (RAS) was studied in 30 patients with renovascular hypertension and 33 patients with essential hypertension. Plasma renin decreased with age in patients with renovascular hypertension and essential hypertension. However, in patients with renovascular hypertension, the change was not statistically significant. Plasma aldosterone concentration showed a tendency to decrease with age in both groups. Stimulated plasma renin activity and the net increase in plasma renin activity after captopril administration in patients with essential hypertension showed a significant decrease with age. In patients with renovascular hypertension, exaggerated response of renin secretion was observed in younger patients, but middle-aged and elderly patients did not demonstrate this hyper-responsiveness. The degree of decrease in blood pressure by administration of an angiotensin (Ang) II analog ([Sar1,Ile8] Ang II) was the same in both younger and elderly patients with either disease. These results suggest that the effect of aging on the RAS occurs not only in patients with essential hypertension, but also in patients with renovascular hypertension. Furthermore, although the Ang II analog infusion test and captopril stimulation test are considered to be useful screening tests for renovascular hypertension, we consider that the combination of Ang II analog test and captopril test may be favorable to screen renovascular hypertension, since the captopril stimulation test had a lower sensitivity in younger (under 35 years old) patients.

Adult↗

PubMedDate not supplied

Increased atrial natriuretic factor secretion after endothelin injection in dogs.

Hemodynamic and hormonal responses to bolus intravenous injections of synthetic porcine endothelin (pET) were examined in anesthetized dogs. There were no significant changes in mean blood pressure (MBP), right atrial pressure (RAP), or plasma atrial natriuretic factor (ANF) concentration in response to 40 pmol/kg of the peptide. However, responses to 400 pmol/kg of the peptide were significant: MBP rose from 114 +/- 6 mmHg (mean +/- SE) to 139 +/- 7 mmHg (p less than 0.01), RAP rose from 5.4 +/- 0.9 mmHg to 7.8 +/- 1.1 mmHg (p less than 0.01), and ANF increased from 45 +/- 10 pg/ml to 277 +/- 33 pg/ml (p less than 0.01). Peak value of RAP was observed 2.6 +/- 0.4 min, while peak of ANF was 11.4 +/- 0.9 min after peptide injection. There was a strongly positive correlation (r = 0.93, p less than 0.01) between the increase in RAP and the increase in ANF in dogs given 400 pmol/kg of pET. These results indicate that exogenously administered pET to anesthetized dogs alters hemodynamics and induces ANP release, and are compatible with a postulate that the ANF release is caused by elevated RAP.

Animals↗

PubMedDate not supplied

Effects of the angiotensin II receptor antagonist, TCV-116, on blood pressure and the renin-angiotensin system in healthy subjects.

TCV-116 is a new, nonpeptide, angiotensin II type-1 receptor antagonist that acts as a specific inhibitor of the renin-angiotensin system. In this study, 36 healthy male volunteers were administered single and repeated oral doses of TCV-116 to investigate its effects on blood pressure and heart rate, and to evaluate the safety and pharmacokinetics of the drug. At single doses of 2.5 mg and greater, TCV-116 significantly lowered blood pressure even in normotensive subjects. This hypotensive effect was maintained during repeated administration on a once-daily regimen over an 8-day period. Serum concentration of M-1, an active metabolite of TCV-116, increased in a dose-dependent manner, reaching a peak 3 to 4 hours after administration. An amount of M-1 equivalent to approximately 10% of the administered dose of TCV-116 was excreted in the urine during the first 24 hours following administration. No accumulation of M-1 was observed in subjects receiving repeated administration of TCV-116. No adverse effects were observed except for mild headache in three subjects. These results suggest that the renin-angiotensin system plays a role in the regulation of blood pressure, even in normotensive subjects, and that TCV-116 may prove to be useful in the treatment of hypertension.

Adult↗

PubMedDate not supplied

Pilot study of a new angiotensin II receptor antagonist, TCV-116: effects of a single oral dose on blood pressure in patients with essential hypertension.

After a 1-week placebo control period, six hypertensive patients (mean age, 67 years) each received single doses of 1, 2.5, and 5 mg of TCV-116 at 2- to 3- day intervals. Systolic and diastolic blood pressures were significantly lower after the final dose (5 mg) of TCV-116 than on the last day of the placebo period. Blood pressures were decreased after each dose of TCV-116 in a dose-dependent fashion from 2 hours after administration and reached a nadir at 4 to 6 hours. After 2.5 and 5 mg of TCV-116, the hypotensive effect was sustained for 24 hours. Pulse rate did not change significantly. Plasma renin activity and angiotensin I levels increased in a dose-dependent fashion after TCV-116, but the changes were not significant. No changes were noted in plasma aldosterone or angiotensin II levels. One patient reported mild light-headedness after 5 mg of TCV-116. No other side effects or abnormal laboratory tests results were noted. It appears that TCV-116 is a safe and effective antihypertensive agent.

Aged↗

PubMedDate not supplied

Antihypertensive efficacy of FK906, a novel human renin inhibitor.

The antihypertensive efficacy of a newly developed orally active human renin inhibitor (FK906) was evaluated in 14 patients with essential hypertension aged 40 to 83 years (mean, 64 years). After a 1-week placebo run-in period, 25 mg of FK906 was given twice daily; this was increased up to 100 mg twice daily until sufficient blood pressure reduction was obtained. No adverse effects were observed in any patients. Supine blood pressure was decreased from 169 +/- 3/97 +/- 1 mmHg to 153 +/- 5/87 +/- 3 mmHg at 25 mg twice daily (n = 14), to 142 +/- 5/78 +/- 3 mmHg at 50 mg twice daily (n = 12), P < 0.01), and to 137 +/- 10/77 +/- 8 mmHg at 100 mg twice daily (n = 6, P < 0.01). The hypotensive effect was sustained over 24 hours. Pulse rate did not change. Plasma renin activity and angiotensin I were decreased after FK906 administration only in patients with increased plasma renin activity. The hypotensive effects of FK906 were not correlated with baseline plasma renin activity. Suppression of the noncirculating tissue renin-angiotensin system may account for the hypotensive action of FK906. The results suggest that FK906 is a promising antihypertensive drug in patients of all ages and with different plasma renin levels.

Adult↗