Is there a common link between the mechanisms of mineralocorticoid-induced and genetic hypertension?

We have shown that (1) mineralocorticoids increase vascular smooth muscle (VSM) membrane permeability to Na+ through a receptor-mediated mechanism as mineralocorticoid-induced hypertension develops, and (2) prehypertensive spontaneously hypertensive rats (SHR) have elevated plasma aldosterone and expanded interstitial fluid volumes, both of which normalize as the rats reach the early hypertensive phase. Others have reported elevation in other mineralocorticoids, VSM membrane permeability changes to Na+ and exaggerated adrenocorticotrophic hormone (ACTH) response to stress in SHR. We hypothesize the SHR have a genetically determined, generalized membrane defect of increased Na+ permeability, not unlike that which is inducible by excessive exogenous mineralocorticoid and which accompanies the hypertension induced by mineralocorticoids. Further, we hypothesize that the insidious onset of hypertension in SHR is at least partly due to the absence or the low activity of Na/Ca exchange in VSM of young SHR, delaying the intracellular accumulation of Ca2+ with its consequent increase in VSM tension. Finally, we predict that the anticipated haemodynamic changes accompanying interstitial fluid volume expansion are not necessary to the development in SHR.