Hirofumi Kino

Atrial Natriuretic Peptide and Antihypertensive Action Due to β-Blockade in Essential Hypertensive Patients

The effects of β-blocker treatment on hemodynamics were studied in relation to plasma atrial natriuretic peptide (ANP) levels in 17 outpatients with essential hypertension. Administration of propranolol for twelve weeks to untreated subjects resulted in a signif icant (P < 0.001) rise in plasma ANP levels (from 37.9 ±21.2 to 66.7 ±46.2 pg/mL, mean ±SD). Systolic and diastolic blood pressures were significantly decreased (P < 0.05 and P < 0.01, respectively). Heart rate was also significantly decreased (P < 0.001). On the other hand, a significant reduction of cardiac index was detected (from 4.12 ±1.34 to 2.96 ±0.75 L/min/m2, P < 0.01) with chronic administration of propranolol, suggesting a reflection of decreased cardiac function. A significant negative correlation was observed between %changes in systolic blood pressure and %changes in plasma ANP (r=-0.594, P < 0.05). These results suggest that the increased plasma ANP levels may contribute to the antihypertensive effect with propranolol.

Significant role of the increase in renin-angiotensin system in cardiac hypertrophy and renal glomerular sclerosis in double transgenic tsukuba hypertensive mice carrying both human renin and angiotensinogen genes.

Tsukuba hypertensive mice (THM) are a hypertensive model prepared by mating a transgenic mice with human renin gene and a transgenic mice with human angiotensinogen gene. In the present study, we examined effects of renin-angiotensin system (RAS) on cardiac hypertrophy and renal disorders using Tsukuba hypertensive mice. While THM showed an increase of about 30 mmHg in systolic pressure compared to C57BL/6 mice employed as normal control animals, the increase in blood pressure was not observed in the mice to which either gene was transferred. Urinary volume, water intake volume, urinary albumin excretion, heart to body weight ratio and renal glomerular sclerosis index increased significantly in THM, but none of these parameters showed a significant difference from the C57 mice when they were examined in mice to which either of the genes was transferred. In contrast, when lisinopril was administered to THM, all the parameters decreased significantly without lowering the systolic pressure. From these findings, it was demonstrated that RAS was playing a significant role in cardiac hypertrophy and renal disorders of THM and that lisinopril had inhibitory effects on cardiac hypertrophy and renal glomerular sclerosis by inhibiting RAS.

EFFECT OF AN ANGIOTENSIN II RECEPTOR ANTAGONIST, TCV‐116, ON NEOINTIMAL FORMATION FOLLOWING BALLOON INJURY IN THE SHR CAROTID ARTERY

1. In the present study, we examined the effect of a novel angiotensin II type I receptor antagonist, TCV‐116, on carotid neointimal formation after balloon injury in SHR and WKY rats.

Effect of lisinopril on deposition of iron in renal tissue in Tsukuba hypertensive mice carrying human renin‐angiotensin system genes

Tsukuba hypertensive mice (THM) are transgenic mice that carry both human renin and angiotensinogen genes and overexpress the human renin‐angiotensin system (RAS). In the present study, the effect of lisinopril on deposition of macromolecular iron in renal tissue in THM was evaluated. Twelve‐week‐old male THM were divided into the following groups: lisinopril dosage group (ACEI group), hydralazine dosage group (hydralazine group), and a no‐drug group (control group). Age‐matched male C57BL/6 mice (wild group) were used as normal controls. Each mouse was treated with a drug for 8 weeks. All mice were euthanised at 20 weeks of age, and their kidneys were fixed and stained with Berlin‐blue. Systolic blood pressure was significantly higher in the control group than in the wild group, and it decreased significantly to similar levels in the ACEI group and the hydralazine group. Iron deposition was observed in proximal renal tubules in the control group and the hydralazine group, but iron deposition was not observed in the ACEI group or the wild group. The results of the study suggest that the RAS plays an important role in the deposition of iron in the proximal renal tubules in THM, and that lisinopril prevents this deposition.

Intramyocardial Ejection of Basic Fibroblast Growth Factor Increased Regional Myocardial Blood Flow Andsalvaged Infarcted Myocardium in Dogs

We studied whether basic fibroblast growth factor (bFGF) might increase regional Myocardial blood flow (Qm) at the infarcted myocardium. In eight dogs, bFGF 300 μg was injected into the myocardium supplied by the left anterior descending coronary artery (LAD), and the artery was ligated. In 12 dogs, saline was injected (control group). Nonradioactive colored microspheres were used to determine Qm. The amount of viable myocardium and the extent of fibrosis in the infarcted area four weeks after occlusion were measured histologically. In the outer layer, the Qm values immediately after and four weeks after occlusion were 26 ± 2% and 70 ± 6%, respectively, in the control group, and 46 ± 5% and 121 ± 13%, respectively, in the bFGF group. The Qm at both times in the bFGF group was significantly higher than the corresponding control group values (p < 0.01). The Qm at four weeks in the inner and middle layers also significantly increased in the bFGF group. There was more viable myocardium (control vs. bFGF group: 41 ± 5% vs. 61 ± 7%, p < 0.05) and less fibrosis (3.1 ± 0.2 vs. 2.0 ± 0.4, p < 0.01) at the outer layer in the bFGF group. bFGF caused a marked increase of the Qm, an increase of viable myocardium, and a decrease of fibrosis at the infarcted myocardium. We conclude bFGF was effective in limiting infarct size in acute myocardial infarction.