Haruhisa Hashimoto

Changes of plasma renin activity by intracerebroventricular administration of biological active peptides in conscious rats

We studied the effects of intracerebroventricular administration of angiotensin II (ANG II), bradykinin (BK), leucine-enkephalin (Leu-ENK) and neurotensin (NT) on plasma renin activity (PRA), blood pressure and heart rate in conscious and unrestrained rats. Five microliters of each peptide solution was injected into the lateral cerebral ventricle. These four peptides all produced pressor effects after intracerebroventricular injection. ANG II and NT significantly suppressed PRA, BK did not affect PRA, and Leu-ENK significantly increased PRA. The central peptidergic stimulation caused by these four peptides increased blood pressures in conscious rats but showed different effects on PRA.

Different Mechanisms Maintaining High Blood Pressure in Chronic One-Kidney, One-Clip, and Two-Kidney, One-Clip Hypertensive Rats

To evaluate the difference of the blood pressure regulating mechanisms of chronic (12-14 weeks) one-kidney, one-clip (1K-1C) and chronic two-kidney, one-clip (2K-1C) hypertensive rats, we administered captopril, captopril plus indomethacin, and indomethacin to the rats. Pretreatment values of plasma renin concentration, plasma aldosterone concentration and urinary kallikrein excretion were significantly higher in 2K-1C than in 1K-1C hypertensive rats. Captopril-induced blood pressure reduction was greater in 2K-1C than in 1K-1C hypertensive rats. When captopril was administered to the rats treated with indomethacin, captopril-induced blood pressure reduction was attenuated only in 2K-1C hypertensive rats. Indomethacin produced renal impairment and further raised the blood pressure in 1K-1C hypertensive rats, but did not in 2K-1C hypertensive rats. These results suggest that the renin-angiotensin system functions to maintain high blood pressure more predominantly in chronic 2K-1C than in 1K-1C hypertensive rats. The renal kallikrein-kinin system is suppressed in chronic 1K-1C hypertensive rats but not in 2K-1C hypertensive rats. The renal prostaglandin system is more important for regulating the renal circulation in chronic 1K-1C than in 2K-1C hypertensive rats.

Reduced Responses of Renin Release to Three Different Stimuli in Essential Hypertensive Patients of Stage II (Who Stage Classification)

The responses of renin release to three different stimuli, such as 1) head-up tilt, 2) administration of loop diuretics(bumetanide) and 3) low sodium diet + administration of bumetanide + ambulation were examined in essential hypertensive patients and normotensive subjects. Essential hypertensive patients were classified as stage I and II according to WHO stage classification. Groups studied were age-matched. The responses of renin release to three stimuli did not significantly differ in normotensive subjects (n = 13, 42 +/- 2(SEM) years old) and essential hypertensive patients of stage I (n = 15, 44 +/- 2). However, essential hypertensive patients of stage II (n = 20, 44 +/- 1) showed significantly lower responses of renin release to all three stimuli than essential hypertensive patients of stage I and normotensive subjects. The results suggest that the suppression of renin release is related in part to the development of hypertension.

An Exaggerated Natriuretic Response to Hypertonic Saline Infusion in the Stage II (WHO Stage Classification) Essential Hypertensive Patients

We examined the natriuretic response to a hypertonic saline infusion in essential hypertensive patients who were subgrouped according to WHO stage classification. We studied 36 essential hypertensive patients and 17 normal subjects matched for age under the precise state of sodium balance (120 mEq sodium per day). The stage II essential hypertensive patients had exaggerated diuretic and natriuretic responses following the infusion of 525 ml of saline containing 120 mEq sodium for 1 hour. Our results suggest that development of essential hypertension induces a functional state that resembles expansion of extracellular fluid volume.