The Role Of Epithelial Sodium Channel And Sympathetic Nervous Potentiation In The Development Of Salt Sensitive Hypertension Among Nigerians In Lagos

ABSTRACT

The mechanisms by which salt causes hypertension are not conclusive. Increased sympathetic activity and systemic vascular dysfunction have both been implicated as well as mutations of the epithelial sodium channel (ENaC) that resulted in increased reabsorption of salt from the distal nephron. However, although an adrenergic overdrive has been observed in some hypertensive patients, it is not clear whether this adrenergic overdrive is the hallmark of hypertension. It has equally been a subject of debate whether exaggerated vascular reactivity is a cause or consequence of hypertension. Also, whereas ENaC mutations especially the β-T594M variant has been related to salt sensitive hypertension among Black individuals living in London, similar associations have not been recorded in AfricanAmericans. On the other hand, among South Africans of black ancestry, some studies have shown no incidence of β-T594M ENaC mutation while a different type of ENaC mutation has been recorded in one study. The present study was therefore designed to determine the role of salt sensitivity, autonomic potentiation and the epithelial sodium channel activity in the development of hypertension among Nigerians. Fifty-three otherwise healthy hypertensive (HT) adults and forty-seven age-matched normotensive (NT) subjects were studied. After baseline parameters had been obtained, the subjects were salt-loaded with 200 mmol/day of Na+ as sodium chloride for 5 days. Thereafter salt sensitivity was determined in all the subjects as ΔMABP ≥ +5mmHg following the salt-loading. As a test of mechanism for salt-sensitivity, plasma Na+ , urine Na+ excretion (UNaV), salt sensitivity index (SSI) and sodium clearance were determined. To assess the effect of the sympathetic nervous system on the cardiovascular system of the subjects, vascular reactivity and forearm vascular resistance (FVR) were determined before and after exposing the subjects to the cold pressor test for one minute. To assess the relationship between ENaC markers and salt sensitivity, the subjects were again salt-loaded with 200mmol/day of Na+ with which 5mg Amiloride was co-administerd for the duration.