Adrenal Response to Angiotensin II in Black Hypertension

Abstract

Abstract-Adrenal responsiveness to angiotensin (Ang) II is markedly blunted in black hypertensive patients compared with white hypertensive patients. One characteristic of this blunted adrenal response in whites is a powerful sexual dimorphism: premenopausal white women rarely show blunted responses. This abnormality, most evident when the system is activated by a low-salt diet, is a cardinal feature of the syndrome of nonmodulation, affecting a large percentage of white hypertensive patients. Nonmodulation is also marked by an increase in cardiovascular risk beyond that from hypertension itself. This study investigated whether young black women are likewise spared its expression or whether the adrenal unresponsiveness common among black hypertensive patients is unaccompanied by a gender bias. We compared the adrenal response to Ang II in 382 hypertensive patients (313 white, 69 black; 238 male, 144 female). Ang II was infused when subjects were in balance on a 10-mmol Na ϩ intake. As anticipated, white hypertensive patients showed a very strong sexual dimorphism, with women having twice the aldosterone response of men (Pϭ0.0001). Blacks, on the other hand, showed no gender difference (Pϭ0.9). Increasing age had the dramatic effect of reducing responsiveness in white women but not in blacks. Young black women demonstrated the same blunting of adrenal responsiveness as older black women and black men of all ages. Mechanisms protecting against a blunted adrenal response to Ang II in young white women are absent in blacks. These differences may contribute to the markedly increased prevalence of hypertension in young black women. Key Words: angiotensin II Ⅲ race Ⅲ gender Ⅲ aldosterone Ⅲ potassium Ⅲ hypertension, renal W e have reported a striking frequency of blunted adrenal responses to angiotensin (Ang) II infusion in black hypertensive patients. 1 Blunting of the adrenal response to Ang II is a cardinal feature of the syndrome of nonmodulation (NM). One additional characteristic of this response in NM is a powerful sexual dimorphism: premenopausal white women rarely show a blunted adrenal response. 2 NM is also marked by an increase in cardiovascular risk factors and cardiovascular risk itself. 3,4 Young black women have up to 3 times the risk for coronary heart disease and death of white women. 5,6 A large degree of this excess risk is attributable to differences in coronary risk factors, including elevated blood pressure. 7,8 This striking racial difference in risk has not been observed among men.Prompted by these observations, we undertook a systematic analysis of adrenal responsiveness in a large cohort of black and white hypertensive patients to test the hypothesis that the sexual dimorphism protecting young white women from phenotypic expression of NM is not present among blacks. The finding that black women have a significantly greater frequency of a blunted adrenal response to Ang II than do young white women may help explain their dramatic increase in cardiovascular risk. MethodsThe data reported in the ...

Dexamethasone and cardiac potassium currents in the diabetic rat

“…There are also indications that secretion, activation or action of glucocorticoids may be gender dependent under some conditions ( Walker et al ., 2000 ; Fisher et al ., 2001 ; Traustadottir et al ., 2003 ).…”

Biological Sex Modulates the Adrenal and Blood Pressure Responses to Angiotensin II

“…Finally, in a small population, we reported that Aldo responses to AngII were greater in women than men with hypertension and likely familially associated 15, 16 . This difference narrows in older subjects and is likewise not observed in hypertensives of African descent 17 . Thus, there remains controversy concerning the relationships between biological sex, Aldo/MR activation and cardiovascular damage.…”

Angiotensinogen Genotype Affects Renal and Adrenal Responses to Angiotensin II in Essential Hypertension

“…Initial candidate genes of interest have been elements of the RAAS, particularly angiotensinogen (AGT), given the generally positive linkage 11 and association 12 of certain AGT polymorphisms with hypertension. Examination of genotypic association, however, is complicated by the recognition that additional factors blunt renal or adrenal responses to infused Ang II, including male sex, 13 black race, 14 diabetes, 15 acute hyperglycemia, 16 obesity, 17 and insulin resistance. 18 We considered these issues in a previous multivariate analysis and found an independent association with the AGT235T polymorphism and reduced renal vasoconstriction in response to infused Ang II.…”