Sexual Dimorphism of Renal .ALPHA.2-Adrenergic Receptor Regulation in Dahl Rats.

Abstract

Male Dahl salt-sensitive hypertensive (S) rats develop hypertension faster than females. We measured renal a2-adrenergic receptor density of inbred Dahl salt-sensitive (SSIJR) and salt-resistant (SR/JR) rats, using [3H]-rauwolscine saturation binding studies. Male and female SSIJR rats were gonadectomized or sham-operated at 6 weeks of age and fed a high salt diet for 4 weeks. Additional intact SSIJR and SRIJR rats of both sexes were fed the high salt diet for a longer period of time (7 weeks instead of 4 weeks). Both blood pressure and renal a2-adrenergic receptor density were significantly higher in male than female SSIJR rats on high salt diet for 4 weeks. Gonadectomy did not change blood pressure nor did it change renal a2-adrenergic receptor density measured at the 4th week of high salt feeding in either male or female SSIJR rats. When the SSIJR rats were fed high salt diet for a longer period (for 7 weeks), blood pressure of female SSIJR reached the level of males, but the density of renal a2-adrenergic receptors was still significantly lower than that of males. Both renal a2-adrenergic receptor density and blood pressure were higher in male than female SR/JR. We conclude that higher blood pressure in male Dahl SSIJR and SR/JR rats is associated with higher renal a2-adrenergic receptor density compared with their female counterparts. (Hypertens Res 1996;19: 83-89) Key Words: receptors, adrenergic, alpha, rauwolscine, Dahl rats Blood pressure is influenced by sex in mice (1), rats (2), and humans (3). Male spontaneously hypertensive rats (SHR) and Dahl salt-sensitive (S) rats develop more severe hypertension than their female counterparts (4-11). Androgen receptors and male hormones potentiate and estrogen attenuates blood pressure in SHR (4-9). In Dahl S rats, however, the sex difference in blood pressure appears to be solely attributed to the ovaries (11). Ely et al. (4) and Turner et al. (5) have demonstrated that a component of SHR hypertension is linked to the Y chromosome, which is partially responsible for the higher blood pressure in males than in females. They have further identified asex-influenced component of hypertension associated with the autosomes in SHR (6). Thus, blood pressure is both sex-influenced and sex (Y)-linked trait in SHR. Notably, male normotensive control Wistar-Kyoto (WKY) (4) and SR/JR rats (12) also have higher blood pressure than their respective females. However, the exact mechanisms whereby sex affects blood pressure is not clear. Ellison et al. (13) found that renal angiotensinogen mRNA concentration in the male WKY is higher than females. Castration lowered the mRNA level by 60%. Chen et al. (14) recently found that sex difference in the reninangiotensin system is present in SHR as well, which may be responsible for the sexual dimorphism of blood pressure in that strain. Several lines of evidence suggests that a2-adrenergic receptors may be involved in the development of the sex difference in blood pressure. For example, infusion of clonidine, an a2-adrenergic ago...

Thick Ascending Limb Sodium Transport in the Pathogenesis of Hypertension

“…Finally, sex differences in Dahl rats have been reported (204,437,754); however, none of these addressed thick ascending limb function.…”

Cardiovascular and metabolic phenotypes in relation to the ADRA2B insertion/deletion polymorphism in a Chinese population

“…Several experimental studies also lend support to gender differences in the regulation of the a2-adrenoceptor and its relation to blood pressure. Indeed, in normotensive and hypertensive rat models, male compared with female animals had a higher blood pressure and an elevated a2-adrenoceptor density in the kidneys [24,25]. Castration of male spontaneously hypertensive rats reduced the malefemale differences in blood pressure and the renal a2adrenoceptor density by 60% [24].…”

Regional differences in sexually dimorphic protein expression in the spontaneously hypertensive rat (SHR)

“…Alpha 2A receptors in the kidney have also been implicated in hypertension [31,[75][76][77]. In SHR and Dahl hypertensive rats renal alpha 2 receptor density, as assessed by radioligand binding studies, was greater in males than females [31,78]. In contrast, we observed that renal alpha 2A receptor expression was decreased in male compared to female SHR.…”