Differential regional haemodynamic changes during mineralocorticoid hypertension.
BACKGROUND
Primary aldosteronism is a cause of hypertension in up to 10% of hypertensive patients, but the mechanisms by which excess aldosterone raises arterial pressure remain unclear.


OBJECTIVE
To investigate the systemic and regional haemodynamic changes during the development and maintenance of aldosterone-induced hypertension and the effect of sympathetic and vasopressin blockade.


METHODS
Responses to intravenous infusion of aldosterone (10 microg/h) for 4 weeks were determined in five conscious sheep. The effects of sympathetic blockade with propranolol and phentolamine or vasopressin V1-receptor blockade with SR59049 were investigated in six further sheep infused with aldosterone.


RESULTS
Aldosterone progressively increased the mean arterial pressure by 20 mmHg over 4 weeks (P < 0.001). The changes in cardiac output were variable between animals, resulting in no overall significant change. Total peripheral conductance was significantly decreased due to selective reductions in mesenteric conductance (from 6.17 +/- 0.27 to 4.46 +/- 0.15 ml/min per mmHg, P < 0.001) and iliac conductance (from 1.54 +/- 0.21 to 1.27 +/- 0.15 ml/min per mmHg, P < 0.001). In contrast, renal and coronary conductance were unchanged and renal blood flow increased from 290 +/- 17 to 350 +/- 28 ml/min (P < 0.01) and coronary blood flow from 34.7 +/- 3.0 to 44.6 +/- 2.5 ml/min (P < 0.05). These aldosterone-induced changes were not inhibited by sympathetic or vasopressin V1-receptor blockade.


CONCLUSIONS
Excess aldosterone caused a slow progressive increase in arterial pressure, which in the long term depended on reduced total peripheral conductance. This resulted from vasoconstriction in the gut and skeletal muscle, but not the kidney. These effects were not mediated by the sympathetic nervous system or vasopressin.
May
Clive N
CN
Howard Florey Institute of Experimental Physiology and Medicine, University of Melbourne, Parkville, Victoria, Australia. c.may@hfi.unimelb.edu.au