The role of renal prostaglandin e and kallikrein in pathogenesis of essential hypertension

The present study was done to investigate the interrelationships between renal kallikrein-kinin, renal prostaglandin E and renin-angiotensin-aldosterone systems in human and the possibility that renal kallikrein-kinin and renal prostaglandin E may participate in the pathogenesis of essential hypertension by means of measuring urinary excretion of kallikrein and prostaglandin E, plasma renin activity and plasma aldosterone concentration before and after stimulation or inhibition of the renin-angiotensin-aldosterone system and inhibition of renal prostaglandin E generation. Urinary kallikrein excretion was increased after the stimulation of the renin-angiotensin-aldosterone system by low Na diet or the administration of furosemide and upright posture, while it tended to decrease after the inhibition of the renin-angiotensin-aldosterone system by the administration of l-sarcosine-8-isoleucine angiotensin II under sodium depletion or spironolactone. These data showed that the changes in urinary kallikrein excretion paralelled with those of the renin-angiotensin-aldosterone system following various stimuli, suggesting that renal kallikrein-kinin system may regulate blood pressure by opposing the action of the renin-angiotensin-aldosterone system. Urinary PGE excretion was decreased after sodium depletion and increased after the administration of furosemide in spite of the augmentation of the renin-angiotensin-aldosterone system. The changes in urinary PGE excretion was closely related to those in urinary Na output after various stimuli and a significant positive correlation was found between basal levels of urinary PGE and those of urinary Na, suggesting that renal prostaglandin E may be involved in the regulation of blood pressure by affecting renal sodium handling. The present data showed that basal level of urinary excretion of PGE and kallikrein was lower in essential hypertension than in normal subjects and that the release of renal kallikrein and PGE after furosemide administration was also suppressed in essential hypertension compared with that in normal subjects, suggesting that there exists an impaired defense mechanism against the renin-angiotensin-aldosterone system resulting in sodium retention.