Project B14

Genetic and environmental contributors to vascular function in primary aldosteronism

The causes of the excessive cardiovascular morbidity in patients with primary aldosteronism (PA) are ill-defined, but likely involve both genetic and environmental factors that modulate both aldosterone secretion and its harmful actions on target tissues. Clinical studies suggest that dietary salt and fat intake are relevant environmental contributors. It is still unknown whether these factors simply aggravate the detrimental effects of aldosterone on vascular structure and function or whether adrenal steroid hypersecretion is further exacerbated by diet.

In the second funding period, we therefore aim at a more granular understanding of the processes which govern vascular remodeling in PA and at defining innovative routes to therapy. Therapeutic advances would very likely be applicable to essential hypertension and, thus, carry a tremendous public health impact.

Specifically, we aim at characterising the interactions between dietary environmental stressors and endogenous hyperaldosteronism. A particular focus will be placed on adrenal as well as cardiovascular effects. We strive to develop pathophysiology-guided therapies to simultaneously address adrenal oversecretion and cardiovascular maladaptive responses.

Aims

(I) Determine the combined impact of mineralocorticoid excess and dietary stress on cardiovascular and adrenal function on a tissue level.

(II) Identify adrenal and vascular cell types affected by aldosterone and environmental stressors.

(III) Establish the utility of novel therapeutic molecular mechanisms addressing tissue-protective mechanosensitive vascular reflexes and normalising adrenal mineralocorticoid output in diet-augmented endogenous hyperaldosteronism.

© SFB/TRR 205