Aim: Exogenous Angiotensin II (Ang II) is currently used for treatment of hypotensive vasodilated shock, despite limited context-specific information about regional circulatory or cardiac responses. We aimed to experimentally investigate sites of action and mechanisms for the cardiovascular acute effects of Ang II infusion with emphasis on regional circulatory control and myocardial systolic and diastolic function. Methods: In healthy anaesthetised pigs, perivascular ultrasound flowmetry, laser-doppler flowmetry and tissue micro-oximetry were employed regionally (kidney and splanchnic organs), while cardiac function was evaluated by left ventricular pressurevolume loop analysis as derived from continuous intracardiac conductance volumetry and tip-manometry. Ang II was administered either systemically (i.v.) or in the left coronary artery in a continuous, dose-variable regimen. Regional perfusion pressures were artificially controlled either by pharmacological (nitroprusside) modulation of systemic arterial pressure or by local arterial graded occlusion (perivascular clamp). Cardiac afterload was controlled by pharmacological (nitroprusside) vasodilation. Results: Ang II exerted similarly powerful vasoconstrictions in the splanchnic and renal circulations. However, the splanchnic vascular bed differed in its responsiveness to Ang II in the sense that concomitant artificial maintenance of systemic normotension fully inhibited the increase in splanchnic vascular tone. Further, splanchnic vasoconstriction by Ang II was potentiated by increases in local arterial pressure. Heart rate and systolic function indices increased dose-dependently by systemic administration of Ang II, regardless of prevailing afterload conditions. Diastolic function was impaired or unchanged. On the other hand, these cardiac effects could not be reproduced when Ang II was administered via the intracoronary route. Conclusions: In the splanchnic vascular bed, the vascular responses of Ang II are powerfully modulated by local vasomotor control. Thus, during concurrent increases in systemic arterial pressure, autoregulatory myogenic increases in vascular smooth muscle tone serves to potentiate the local vasoconstrictive actions of Ang II. This implies that blood pressure alterations have an important role for the prediction of changes in splanchnic vascular resistance during Ang II treatment. Cardiac effects of Ang II include increases in contractile function, but seem to be predominantly mediated via extracardiac structures and mechanisms. This implies that the integrity of remote mechanisms for control of myocardial function are important for the cardiac effects of Ang II treatment. Keywords: Renin-Angiotensin System, Angiotensin II, Angiotensin Amide, Nitroprusside, Swine, Conductance volumetry (non-MESH), Cardiac function, Systolic function, Diastolic function, Vasoconstriction, Splanchnic Circulation, Renal Circulation
Umeå: Umeå University , 2001.