Seiji Gotoh

Levels of plasma 6-keto-PGF1α in normotensive and essential hypertensive males with and without a family history of hypertension

Prostacyclin may act physiologically as an antihypertensive hormone. It remains uncertain, however, whether prostacyclin may be involved in the etiology of primary hypertension. As an index of prostacyclin production, we measured the levels of venous plasma 6-keto-PGF1 alpha by specific radioimmunoassay after silicic acid column chromatographic purification in 31 normotensive and 36 hypertensive males. The subjects were grouped according to the presence or absence of a family history of hypertension, and matched for age and blood pressure. Levels of 6-keto-PGF1 alpha in normotensive males with a family history of hypertension (12.0 +/- 1.7 pg/ml; mean +/- SEM; n = 18) were lower than in normotensive males without a family history of hypertension (17.7 +/- 2.0 pg/ml; n = 13) (p less than 0.01). Levels of plasma 6-keto-PGF1 alpha in hypertensive males with a family history of hypertension (10.2 +/- 1.2 pg/ml; n = 15) were lower than in hypertensive males without a family history of hypertension (20.5 +/- 1.5 pg/ml; n = 21) (p less than 0.005). The levels of plasma 6-keto-PGF1 alpha in males with a family history of hypertension may be decreased genetically. The decrease in production of prostacyclin in males with a family history of hypertension may be a factor in the etiology of hypertension.

Effect of captopril on renal vascular resistance, renin, prostaglandins and kinin in the isolated perfused kidney

Vasodilatory and natriuretic effects of captopril were studied in the isolated hog kidney perfused with modified Krebs-Ringer solution. Renal arterial infusion of captopril caused increases in releases of renin, prostaglandins (PGE2, 6-keto-PGF1 alpha and PGF2 alpha) and kinin, and was accompanied by a decrease in the renal vascular resistance and an increase in urinary sodium excretion. Indomethacin administered with captopril diminished the saluretic effect of captopril and evoked an increase in kinin, but was associated with a marked decrease in prostaglandin and renin releases, while renal vascular resistance remained decreased. Indomethacin alone did not alter vascular resistance and kinin; however, renin and prostaglandin releases were decreased. Aprotinin administered with captopril showed a decrease in releases of prostaglandins, renin and kinin without any change in vascular resistance. These results suggest that increased release of kinin induced by captopril contributes to a reduction in renal vascular resistance. Increased prostaglandin release after captopril administration may be caused by an increase in kinin without direct involvement of captopril in prostaglandin synthesis. Renal prostaglandins may enhance sodium excretion and mediate renin secretion in captopril perfusion.

Effect of prostacyclin infusion on active and inactive renin release in the isolated perfused kidney

The effect of prostacyclin infusion into the renal artery of the isolated perfused hog kidney on the release of active and inactive renin was investigated. Infusion of prostacyclin at a rate of 0.1 microgram/min resulted in a significant increase (p less than 0.01) in active renin and a significant fall (p less than 0.01) in inactive renin. Prostacyclin also increased urinary kallikrein excretion (p less than 0.05). The results indicate that the kidney secretes not only active renin but also inactive renin, and suggest that prostacyclin stimulates the conversion of inactive renin to the active form through the activation of the renal kallikrein system.

Effect of three angiotensin II antagonists, [Sar1, Thr8]-, [Sar1, Ile8]-and [Sar1, Ala8]angiotensin II on blood pressure and endocrine factors in normal subjects

SummaryThe biological effects of 1-Sarcosine, 8-Threonine angiotensin II ([Sar1, Thr8]ANG II) on blood pressure, plasma aldosterone concentration (PAC) and plasma renin activity (PRA) were investigated in six normal subjects on an unrestricted diet, and compared with those of 1-Sarcosine, 8-Isoleucine ANG II ([Sar1, Ile8]ANG II) and 1-Sarcosine, 8-Alanine ANG II ([Sar1, Ala8]ANG II). All three ANG II analogues (A II A) showed agonistic pressor activity, that of [Sar1, Ile8]ANG II being greater than that of [Sar1, Thr8]ANG II or [Sar1, Ala8]ANG II. The antagonistic effect of [Sar1, Thr8]ANG II on blood pressure was less than [Sar1, Ile8]ANG II or [Sar1, Ala8]ANG II. Both [Sar1, Ile8]ANG II and [Sar1, Ala8]ANG II increased PAC and blocked the steroidogenic action of ANG II, while [Sar1, Thr8]ANG II showed little effect on PAC. All three A II A caused similar suppression of PRA and showed no inhibitory effect on the decrease in PRA produced by ANG II. These results indicate that [Sar1, Thr8] ANG II is an A II A with weak agonistic pressor action and that it has vascular selective properties. It is also suggested that ANG II receptors in a variety of target organs are heterogeneous.

Synergic effects of kallikrein-kinin and prostaglandins on renin release on infusion of isolated hog kidney with aldosterone

The effects of infusion of a large amount of aldosterone into the renal artery of isolated perfused hog kidney on the release of renin, prostaglandins (PG) and kinin and the excretion of urinary kallikrein were investigated. Infusion of aldosterone at a rate of 100 ng/min (100 to 800 ng/ml of perfusate) resulted in significant releases of renin, PG (PGE2 , 6-0-PGF1 alpha), and kinin and increase in urinary kallikrein. Infusion of aldosterone and an inhibitor of kallikrein, aprotinin, decreased the releases of renin, PG and kinin and infusion of aldosterone with indomethacin decreased the release of PG but increased that of kinin and urinary kallikrein without significant change in renin releases. These findings suggest that the release of renin by aldosterone may result from synergic effects of renal PG and the kallikrein -kinin system.