Effect of inhibition of peptidase activity on distribution of intrarenal blood flow

Abstract

Experiments were performed in dogs to determine the effects of the intravenous administration of the dipeptide hydrolase inhibitor SQ 20,881 on renal hemodynamics, intrarenal blood flow distribution, and renal function. Dipeptide hydrolase converts angiotensin I to angiotensin II and inactivates bradykinin. SQ 20,881 causes an inhibition of the vasoconstrictor response after angiotensin I and potentiation of the vasodilatory activity of bradykinin. Total renal blood flow, cortical distribution of blood flow, and glomerular filtration rate were determined. In seven animals administration of SQ 20,881 (1 mg/kg) resulted in a decrease in mean systemic blood pressure of 11 mmHg, an increase in total renal blood flow of 0.71 ml/min per g, and a significant fall in glomerular filtration rate. Fractional blood flow to the superficial cortex decreased and to the juxtamedullary cortex increased. Absolute flow was unchanged in the superficial cortex and increased significantly in the deep cortex. The findings are compatible with reported effects of bradykinin on intrarenal blood flow distribution, although the experiments do not distinguish between potentiation of bradykinin or inhibition of angiotensin I conversion.

Effect of ACE-inhibition on tissue blood flow during acute left ventricular failure in the dog

“…The vasodilatation seems to take place in the inner and middle cortical layer. In this respect we can confirm the findings of Bailie and Barbour [2] and Mimran et al [20]. Again, however, we would like to draw attention to possible methodologic artifacts in the results of intrarenal flow distribution.…”

“…Cerebral frontal cortex (2), right ventricle (4), left ventricle (4), lung (2), liver (2), pancreas (3), spleen (3), stomach (2), jejunum (1), colon (1), adrenal (2), kidney (2), renal medulla (6), renal cortex divided in inner (6), middle (6), and outer layer (6), fat (2), skin (2) and muscle (6). A detailed description of the sampling procedure is given in Appendix A.…”

Mechanism of postarrhythmic renal vasoconstriction in the anesthetized dog.

“…During maximal postarrhythmic renal vasoconistrictioni (4 min) renal capsular catecholamines were threefold higher than femoral arterial levels. Comparison of changes in femoral arterial catecholamine levels in these six dogs in response to atrial fibrillation revealed no significanit difference from those seen in the nine animals reported in Table II. The changes from preintervention control hemodvnamics to control hemodynamiiics during an intervention (SQ 20881, phentolamine, propranolol, vagal cooling, atropine renal denervation, bretylium, and hexamethonium) were the same as have been previously reported in the pentobarbital-anesthetized dog and will not be discussed further unless appropriate to the focus of this study (10)(11)(12)(13)(14). tribution of blood flow have been observed in response his study caused a dis-to exercise in the conscious dog with complete heart ion of renal blood flow block (15).…”

Effects of SQ 20,881 on the intact kidney of dogs with two-kidney, one clip hypertension.

“…Therefore, dissociation between sodium excretion and GFR under circumstances of increased and decreased All levels might suggest the involvement of an additional factor, possibly activation of the kallikreinkinin system. 22 In RHT dogs, both All and CEI caused significant natriuresis apparently resulting from different effects on the renal circulation. While in hypertensive animals a decrease in pre-and postglomerular resistance appears to be the most likely cause for the sodium diuresis produced by CEI, an increase in postglomerular capillary pressure may account for the results obtained with infusion of angiotensin II.…”