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Biomedical subjects

J Higaki

Publications and source records attributed to J Higaki.

257 records · Page 15Linked to original sources
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

Long-term effects of pravastatin on serum lipid levels in elderly patients with hypercholesterolemia.

The purpose of this study was to evaluate the long-term efficacy and tolerability of pravastatin, a 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitor, in elderly patients with hypercholesterolemia. Pravastatin was administered for 12 months at a mean final dose of 9.9 mg/d to 208 elderly patients (mean [+/- SD] age, 70 +/- 7 years) with levels of total serum cholesterol greater than 5.69 mmol/L. The mean total cholesterol level was significantly decreased from 6.85 +/- 0.80 mmol/L to 5.59 +/- 0.70 mmol/L after 3 months, and this decrease was maintained thereafter. A similar change was observed in the mean serum level of low-density lipoprotein cholesterol. Although the mean serum level of high-density lipoprotein cholesterol in all the patients did not change significantly, the level in 34 patients with a value lower than 1.03 mmol/L was significantly increased after 3 months and thereafter. The serum level of triglycerides in all patients was significantly decreased after 3 months and thereafter and the decrease was more marked in 101 patients with levels greater than 1.73 mmol/L. In 168 elderly patients receiving 10 mg/d of pravastatin, there were significant negative correlations between the percent decrease in total cholesterol and both baseline total serum cholesterol level (r = -.354, P < 0.001) and age (r = -.208, P = 0.007). No serious side effects were observed. These results indicate that long-term administration of pravastatin is beneficial in the treatment of hypercholesterolemia in elderly patients.

Aged↗
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

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↗