An approach to the evaluation of genetic influences on factors that regulate arterial blood pressure in man.

Abstract

SUMMARY To assess the influence of heredity on factors that help regulate the arterial blood pressure in man, we conducted sodium-loading and depletion studies in monozygotic and dizygotic twins, normotensive first-degree relatives of essential hypertensives, and in nonnotenslve control subjects matched for age, sex, and race. Following sodium-loading, we found evidence for the influence of genetic variance on the natriuretic responses, plasma renin activity (PRA), plasma aldosterone concentrations (PA), and plasma and urinary norepinephrine. Relatives of hypertensives differed from controls in that they had higher blood pressures, greater renin values, and relatively sluggish natriuretic responses. Since renin and fractional sodium excretion values were inversely correlated in all subject groups, it is possible that the heritable influences we observed on sodium excretion were mediated by the renin-angiotensin-aldosterone system. 79 the nature of these influences has not been defined clearly. To examine inherited mechanisms that may contribute to the development of essential hypertension in some individuals, or the resistance to hypertension in others, we conducted detailed studies of monozygotic and dizygotic normotensive twins, normotensive firstdegree relatives of essential hypertensives, and large numbers of normotensive white and black subjects by means of a standardized protocol incorporating both sodium-loading and depletion. "14 In these studies we examined electrolyte balance, components of the renin-angiotensin-aldosterone system, and humoral indicators of sympathetic nervous system activity. The studies in twins 1-34fluences in each of these areas. The studies in normotensive, first-degree relatives of essential hypertensives indicated the existence of important differences in electrolyte excretion and peripheral renin values that may contribute to the susceptibility to hypertension of this high-risk group." We present these findings in light of their bearing on the importance of heredity in regulating blood pressure in man. Methods Studies in TwinsData from monozygotic (MZ) and dizygotic (DZ) twins provide a unique opportunity to test for the existence of genetic variation in traits. Since MZ twins are genetically identical and DZ twins are related as full siblings, a given trait would be expected to exhibit smaller twin-pair differences for MZ than DZ twins if genetic influences are present. On the other hand, if the trait is only influenced by environmental variability, the MZ and DZ twin-pair differences should be approximately equal.The statistical methods involved in the analysis of MZ and DZ twin data have been recently reviewed by Christian. 16 We chose the comparison of MZ and DZ twins as the most efficient method for the initial investigation of heritable components in quantitative by guest on May 11, 2018 http://hyper.ahajournals.org/ Downloaded from

Blood pressure in blacks. Twin studies in Barbados.

“…This is similar to what has been reported by the Indiana group using white adult twins 23 and adult twins and their families. 24 Schicken et al 25 have recently reported similar results in white twin children (age, 11 years) living in Virginia.…”

Salt Sensitivity of Blood Pressure

“…Analogously, there were indirect clues suggesting genetic determination of SSBP: The trait was reproducible when measured with different methods 4 or when repeatedly measured over time 5 ; concordance in characteristics associated with the SSBP phenotype (eg, magnitude of natriuresis and BP and plasma renin responses after salt depletion) was shown in nontwin 6 and twin 7 siblings; and other demographic, clinical, and biochemical characteristics clustered with the SS phenotype. However, it was not until the development of inbred strains of rodents (described below) homogeneous for SSBP or salt resistance of BP that definitive proof of a genetic component was provided.…”

Integrating Drug Pharmacokinetics for Phenotyping Individual Renin Response to Angiotensin II Blockade in Humans

“…18 Renin levels have been shown to be heritable in sodium-loading and depletion studies performed in monozygotic and dizygotic twins and relatives of patients with essential hypertension. 19 Finally, in a large multicenter study, the analysis of 175 hypertensive white subjects from 86 families (71 pairs, 15 trios) showed plasma renin concentrations to be highly correlated between hypertensive siblings on highand low-salt diets after adjustment for age, sex, and natriuresis. 20 However, the genes involved in this familial resemblance have yet to be identified.…”