Possible Influence of Intrarenal Generation of Kinins on Prostaglandin Release From the Rabbit Perfused Kidney

Abstract

The effects of bradykinin and kininogen on renal prostaglandin release were studied in rabbit isolated kidneys perfused with oxygenated Krebs solution. The concentration of prostaglandin‐like material in kidney effluent was determined by bioassay after extraction of the samples with organic solvents. In 7 experiments the samples were assayed after separation of prostaglandins E and F by thin layer chromatography. Addition of bradykinin to the perfusing fluid increased the venous and urinary effluxes of prostaglandin E‐like substance by sixfold and fivefold, respectively, but efflux of prostaglandin F‐like material was unaffected. Addition of kininogen to the perfusing fluid augmented the venous and urinary release of prostaglandin E‐like substances by fifteenfold and ninefold respectively and caused a twofold increase in the efflux of prostaglandin F‐like material into the venous effluent. Aprotinin, a kallikrein inhibitor, reduced the prostaglandin releasing action of kininogen but not of bradykinin. In contrast, inhibition of prostaglandin synthesis by indomethacin suppressed the release of prostaglandin evoked by either bradykinin or kininogen. This study suggests that augmented release of prostaglandins in response to kininogen is a consequence of renal generation of kinins. Thus, changes in the intrarenal activity of the kallikreinkinin system may modulate renal prostaglandin release.

Exaggerated prostaglandin biosynthesis and its influence on renal resistance in the isolated hydronephrotic rabbit kidney.

“…Indomethacin also enhanced and prolonged the AII-induced vasoconstriction (Fig. 4 and Table II (29,30). It excretes sodium in the same concentration as that of perfusate and does not concentrate urine.…”

Interrelations of the renal kallikrein-kinin system and renal prostaglandins in the conscious rat. Influence of mineralocorticoids.

“…Thus, bradykinin stimulates release of a prostaglandin E-like substance into renal blood, 5 and kinins generated intrarenally increase the venous and urinary effluxes of E prostaglandins from the isolated rabbit kidney perfused with Krebs solution. 6 The renal kallikrein-kinin and prostaglandin systems may be instrumental in buffering the …”

“…Thus, bradykinin stimulates release of a prostaglandin E-like substance into renal blood, 5 and kinins generated intrarenally increase the venous and urinary effluxes of E prostaglandins from the isolated rabbit kidney perfused with Krebs solution. 6 The renal kallikrein-kinin and prostaglandin systems may be instrumental in buffering the sodium-retaining action of mineralocorticoids for the following reasons. First, kinins and prostaglandin E2 (PGE2), the major product of prostaglandin synthesis in the renal medulla, share the ability to effect natriuresis and renal vasodilation.…”

Role of prostaglandins in hypertension

“…Thus, several reports indicate their important role in the normal blood pressure regulation mechanisms and they may be involved in electrolyte balance. 25 For instance, the blockade of bradykinin breakdown and enhancement of PGs release probably participate in the antihypertensive effect of ACE inhibi- tors 17,[26][27][28] (Figure 2), diuretic therapy at long range, 29 calcium channel-blocking agents and angiotensin II receptor blockers (AT 1 blockade) 9,19,30,31 among others, as well as the pathogenic mechanism of some diseases such as acute nephritic syndrome where ACEIs are beneficial by increasing bradykinin and PGs survival. 32,33 Obesity and diabetes are marked by increased incidence of hypertension (HT), and elevated levels of FA or their P 450 oxygenated metabolites may contribute to this association.…”