Coronary microvascular fluid flux and permeability: influence of angiotensin II, aldosterone, and acute arterial hypertension.

Vascular permeability of the coronary and mesenteric circulation is increased in association with the arterial hypertension that accompanies either endogenous activation of the renin-angiotensin-aldosterone system (RAAS) or exogenous administration of angiotensin II (AII). Whether this occurs as a result of increased intravascular pressure or of elevations in plasma concentrations of AII or aldosterone (ALDO) (or both) is unclear. This acute study of filtration-independent coronary fluid exchange and macromolecular permeability was undertaken to address these issues in open-chest, anesthetized dogs. The influence of arterial hypertension, with or without associated elevations in plasma AII or ALDO (or both), on coronary permeability was examined by monitoring the response in cardiac lymph flow, protein concentration, and capillary and intramural coronary artery structure. Experimental groups received a 90-minute intravenous infusion of either AII (n = 8), methoxamine (MX; n = 7), or ALDO plus MX (n = 5) in equipotent doses that raised arterial pressure to comparable levels. When we compared these animals with normotensive, instrumented controls (n = 5), we found that (1) lymph flow was a function of arterial and microvascular pressures in each group; (2) increased protein permeability, myocardial edema, extravasated red cells, and infused colloidal carbon were found in both ventricles with AII, together with endothelial discontinuities and enhanced abluminal capillary endothelial vesicle formation, when plasma ALDO had risen significantly in response to AII; and (3) macromolecular permeability was no different from that in controls after MX or ALDO plus MX. Based on this short-term study of acute arterial hypertension, we would conclude that acute elevations in microvascular pressure increase fluid flux, whereas increased circulating effector hormones of the RAAS, not plasma ALDO or hypertension alone, alter coronary microvascular structure and permeability to macromolecules Responsible mechanisms remain to be defined.