Cardiac angiotensinogen and its local activation in the isolated perfused beating heart.

摘要: Increasing evidence suggests that the renin-angiotensin system modulates cardiovascular homeostasis both via its circulating, plasma-borne components and through locally present, tissue-resident systems with site-specific activity. The existence of such a in heart has been proposed, based on biochemical studies as well demonstration renin angiotensinogen messenger RNA cardiac tissue. We conducted present study to determine whether biologically active angiotensin peptides may be cleaved within from angiotensinogen. Isolated, perfused rat hearts were exposed infusions purified hog renin; coronary sinus effluent was collected subsequently assayed for I (Ang I) II II) by high-pressure liquid chromatography specific radioimmunoassay. Both Ang undetectable under control conditions but appeared promptly after addition renin. Dose-dependent peak values release ranged 2.42 +/- 0.65 fmol/min 1.38 0.18 pmol/min during at concentrations between 10 microunits/ml 5 milliunits/ml. levels measured perfusate reflected mean fractional intracardiac conversion 7.18 1.09%. Generation inhibited presence inhibitors converting enzyme, respectively. To investigate source angiotensinogen, we spontaneous isolated hearts. In absence perfusate, initially released high, rapidly declining, low, stable, rate. Prior perfusion angiotensinogen-rich plasma resulted enhanced early did not alter second, delayed phase, suggesting that, plasma-derived substrate, produced also participate formation angiotensin. Supporting this interpretation, animals pretreated dexamethasone showed increased rates only late phase. Our newly demonstrates formed which appears derived part circulating pool endogenous synthesis. These findings add support concept functionally integrated emphasize potential physiological pathological relevance.