Exogenous Angiotensin II Research Articles

Effect of exogenous angiotensin-II on local blood flow in kidneys with neoplasm. Experiments in the rat.

The effect of angiotensin-II on the local renal blood flow and arterial blood pressure was investigated in the rat with the H2 gas washout technique. Increasing intravenous infusion rates gave a decreasing blood flow and increasing blood pressure, renal vascular resistance being close to proportional to the log of infusion rate. In kidneys with experimental neoplasm, the flow reduction was proportionally less in the tumor than in intact renal tissue. The respective flow levels were maintained for 10 to 45 min without tendency to change.

Glomerular adaptations to chronic dietary salt restriction or excess.

Micropuncture studies were performed in 33 Munich-Wistar rats maintained chronically either on dietary NaCl restriction (group 1) or excess (group 2). Values for single nephron (SN) and total kidney glomerular filtration rate (GFR) were identical in both groups. Nevertheless, because of preferential efferent vasoconstriction, glomerular capillary hydraulic pressure (PGC) was higher in group 1, offsetting the lower initial glomerular plasma flow rate (QA) also found in group 1. The pressor response to infusion of exogenous angiotensin II (AII) was less in group 1 than in group 2, suggesting that vascular receptors for AII may have been occupied by endogenous hormone, the latter leading to the efferent arteriolar vasoconstriction. In addition to AII, prostaglandins also appear to be involved in the adaptations of the glomerular microcirculation to chronic variations in salt intake. In group 1, indomethacin or meclofenamate infusion mimicked exogenous AII, causing declines in QA and SNGFR. These changes were lacking in group 2. Because of relative contraction of plasma volume, the vasodilatory effects of prostaglandins appear to be needed in low salt animals to sustain SNGFR and QA. In the high salt group, however, since plasma volume is not contracted, maintenance of SNGFR and QA appears to be less critically dependent on endogenous prostaglandins.

Mechanism of angiotensin I converting enzyme inhibition by SQ20,881 (less than Glu-Trp-Pro-Arg-Pro-Gln-Ile-Pro-Pro) in vivo. Further evidence for extrapulmonary conversion.

The mechanism by which the angiotensin I (AI) converting enzyme inhibitor SQ20,881 (less than Glu-Trp-Pro-Arg-Pro-Glu-Ile-Pro-Pro) blocks the pressor response to exogenous AI was studied in vivo in the intact anesthetized dog. When administered as a single dose 250 times that of injected AI (250 nmoles/kg) into either the pulmonary or systemic circulation, SQ20,881 produced inhibition of pulmonary conversion of exogenous AI to AII that lasted for more than 6 hours as judged by the absence of immunoreactive or labeled AII in the pulmonary venous effluent. In contrast, the pressor response to exogenous AI began to reappear within 1 hour of SQ20,881 administration. Six hours following SQ20,881, the pressor response to AI had nearly returned to normal, still in the absence of demonstrable intrapulmonary conversion and without release of detectable amounts of AII into the pulmonary venous effluent. These experiments demonstrated that AI has a pressor effect in the presence of SQ20,881 that is independent of pulmonary conversion. Studies with (Des-Asp) AII and (Des-Asp, Arg) AII showed that the delayed pressor response to AI following SQ20,881 administration could not be accounted for by circulating peptide metabolites of AI or AII. A competitive inhibitor of AII, (D-Asp, Ile) AII completely blocked the returning pressor response, suggesting that extrapulmonary generation of AII was responsible. The data strongly suggest that the systemic vascular bed taken as a whole contains large amounts of AI converting enzyme that is capable of rapid generation of AII without releasing the peptide into circulation. The extrapulmonary enzyme is more resistant to long-lasting blockade by SQ20,881 than pulmonary converting enzyme. The physiological role of extrapulmonary conversion systemic and local circulatory homeotasis remains to be assessed.

Effect of exogenous and endogenous angiotensin II in the isolated perfused rat kidney.

Rat kidneys were perfused with an artificial solution at constant pressure. The infusion of angiotensin II (AII) (1.5--6 ng min-1) reduced renal perfusate flow (RPF) from 36.6 +/- 2.4 to 19.3 +/- 1.4 ml min-1 (P less than 0.001) (n = 13); GFR rose from 0.48 +/- 0.06 to 0.63 +/- 0.04 ml min-1 (P less than 0.05), and filtration fraction (FF) rose accordingly from 0.015 +/- 0.002 to 0.033 +/- 0.003 (P greater than 0.01). The same results were obtained with purified renin substrate (synthetic tetradecapeptide, 100 ng min-1, n = 8); RPF fell from 31.5 +/- 2.9 to 17.2 +/- 2 ml min-1 (P less than 0.001), GFR rose from 0.36 +/- 0.05 to 0.51 +/- 0.04 ml min-1 (P less than 0.05), and FF increased from 0.021 +/- 0.002 to 0.034 +/- 0.006 (P less than 0.01). The effects of renin substrate were completely prevented by the converting enzyme inhibitor SQ 20,881 (3 X 10(-5) M). In another six experiments the effects of renin substrate at the same dose were fully reversed by addition of the analogue [Sar1,Ala8]AII. We interpret these findings to indicate that both exogenous and endogenous AII produce preferential vasoconstriction of the efferent arteriole, increasing the driving force for ultrafiltration and thereby maintaining or increasing GFR in the face of a reduced plasma flow.