Shuichiro Yasuhara

Participation of Vascular Prostacyclin for the Pathogenesis of Experimental Glucocorticoid Hypertension in Rats

Prostacyclin (PGI2) generation in the mesenteric arteries from dexamethasone acetate (DX) and deoxycorticosterone acetate (DOCA) treated rats was assessed by ex vivo perfusion method. PGI2 generation which was measured by 6-keto-PGF1 alpha output in the perfusate was significantly reduced in DX treated rats at prehypertensive stage both under the basal conditions and in response to angiotensin (ANG) II, whereas in DOCA group rats, vascular PGI2 production was not impaired. Plasma renin activity (PRA) was significantly suppressed in DOCA but normal in DX rats. These results suggest that the reduced PGI2 generation in the resistance arteries may contribute to the development of hypertension induced by DX.

Long-Term Effects of Converting Enzyme Inhibitors on Split Renal Function in Renovascular Hypertension

Long-term effects of angiotensin converting enzyme inhibitors on split renal function were studied using a noninvasive radioisotopic method in five patients with renovascular hypertension. In the stenotic side the glomerular filtration rate which acutely decreased following captopril, tended to return toward pretreatment levels on prolonged captopril administration (up to 2 years), while the value remained unchanged in the nonstenotic side of the kidney. Effective renal plasma flow increased in both sides. During long-term captopril treatment, there were no significant changes in serum creatinine, sodium, potassium, and blood pressure control was maintained at the same level in an acute period. These results suggest that the glomerular filtration in the stenotic kidney of renovascular hypertension, which was acutely reduced, will not further deteriorate, but will increase after prolonged captopril treatment.

The role of prostaglandins for norepinephrine clearance in borderline hypertension

Studies were done to determine the role of endogenous prostaglandins (PGs) for norepinephrine (NE) clearance in 10 male borderline hypertensives (BHT) (age: 20-28) and six age-matched male normotensives (NT). Two experimental protocols were followed in these subjects: 10 min orthostasis with blood sampling (protocol I), and 100 ng/kg/min of L-NE infusion for 60 min at supine position. Blood was collected from indwelling catheter at every min for 10 min after stopping the NE infusion (protocol II). Plasma NE was measured by THI method using HPLC. Disappearance curve of plasma NE was analyzed following the two compartment open model. The orthostasis and the steady state NE infusion were repeated after 150 mg/day of indomethacin (Ind) for three days. There were significant increases in plasma NE after orthostasis in both groups: from 180.8 +/- 28.0 pg/ml to 346.2 +/- 78.0 pg/ml (p less than 0.05) in NT and from 120.1 +/- 12.8 pg/ml to 289.6 +/- 20.3 pg/ml (p less than 0.001) in BHT, but there were no significant differences between the two groups. Ind pretreatment did not alter these responses. The calculated half-time of the first exponential phase (T 1/2) was 1.50 +/- 0.07 min in NT which decreased to 0.98 +/- 0.10 min (p less than 0.05) after Ind pretreatment. In BHT, T 1/2 was 1.03 +/- 0.08 min (p less than 0.01 vs NT), which was not significantly changed after Ind. These results may suggest that endogenous PGs have some role(s) in NT for NE clearance, probably exerting inhibitory action on neuronal uptake. In BHT, neuronal uptake of NE is increased, probably due to an adaptation mechanism to elevated blood pressure.