Male spontaneously hypertensive rats (SHR) have higher blood pressure than females. We compared renal ct 2 -adrenergic receptor density among intact SHR and Wistar-Kyoto (WKY) rats of both sexes, male and female SHR gonadectomized at 4 weeks of age, and gonadectomized SHR supplemented with testosterone. Additional groups of SHR were treated with enalapril (30 mg/kg per day), an angiotensinconverting enzyme inhibitor, from 5 to 14 weeks of age. Renal a 2 -adrenergic receptor density was higher in males than females in both SHR and WKY rats. Female SHR and WKY rats had identical low renal a 2 -adrenergic receptor density. Castration of male SHR reduced the male-female differences in blood pressure and renal a 2 -adrenergic receptor density by 60%. 5 Thus, altered density of renal a 2 -adrenergic receptors might be expected to affect salt and water balance and blood pressure.Renal a 2 -adrenergic receptors are overexpressed in several animal models of genetic hypertension, including the spontaneously hypertensive rat (SHR), 68 Dahl salt-sensitive hypertensive rat, 9 Sabra hypertensive rat, 10 and New Zealand genetically hypertensive rat, 11 when compared with their respective normotensive control strains. The overexpression of renal a 2 -adrenergic receptors occurs as early as 3 weeks of age in SHR compared with Wistar-Kyoto (WKY) rats, an age when blood pressure is not yet different.6 High dietary salt further elevates blood pressure, which parallels an increase in the density of these receptors in SHR. 78 This overexpression of renal a 2 -adrenergic receptors in genetically hypertensive rats probably represents a genetic abnormality because renal a 2 -adrenergic receptor density is not increased in nongenetic forms of hypertension, such as two-kidney, one clip hypertension; one-kidney, one clip hypertension; and deoxycorticosterone acetate-salt hypertension.12 However, it remainsReceived June 23, 1993; accepted in revised form January 4, 1994.From the Department of Medicine, Creighton University School of Medicine, Omaha, Neb.Correspondence to William A. Pettinger, MD, Creighton University School of Medicine, 601 N 30th St, Suite 6730, Omaha NE 68131.with testosterone raised blood pressure and renal a r adrenergic receptor density to the intact male levels in both gonadectomized males and females. Treatment with enalapril decreased blood pressure but not renal <* 2 -adrenergic receptor density in both male and female SHR. We conclude that (1) both renal o 2 -adrenergic receptor density and blood pressure are influenced by sex in SHR and WKY, (2) renal a 2 -adrenergic receptor density like blood pressure is regulated by androgens, and (3) increased renal a 2 -adrenergic receptor density is not a consequence of high unresolved whether the increased renal a r adrenergic receptor density is a cause or a consequence of high blood pressure in genetically hypertensive rats.Interestingly, not one of the aforementioned studies has investigated the role of a potential difference in renal a 2 -adrenergic recept...

It is known that adults with autosomal dominant polycystic kidney disease (ADPKD) have an increased incidence of cardiovascular abnormalities, including mitral valve prolapse. The cardiac manifestations of ADPKD in the pediatric population have not been well established. To determine the cardiac manifestations of children with ADPKD, echocardiography was performed in 154 children of 66 families in which one parent has ADPKD. Eighty-six affected children and 68 unaffected children were evaluated in a prospective, single-blinded manner by echocardiography. Affected children were defined as those with any cysts on a concurrent renal ultrasound or those predicted to be gene carriers by gene linkage analysis. A 12% incidence of mitral valve prolapse was found in the affected children compared with only 3% of the unaffected children (P < 0.05). ADPKD children, but not their unaffected siblings, demonstrate a significant correlation between left ventricular mass index and systolic blood pressure. Moreover, hypertensive ADPKD children have significantly larger left ventricular mass index than do normotensive ADPKD children. A 3.5% incidence of congenital heart disease was found in the affected group, whereas 2.9% of the unaffected children had congenital heart disease. It was concluded that systemic manifestations of ADPKD, particularly cardiovascular abnormalities, are present even in childhood and these warrant the clinician's attention.

The results of classical segregation analysis on 159 families with polycystic kidney disease (PKD) are presented. It had been previously estimated that about 95% of autosomal dominant PKD (ADPKD) families have PKD1, the gene localized to chromosome 16p. The main purpose of the study was to determine if PKD shows any segregation distortion and to obtain new estimates of the age-dependent penetrance. Penetrance at the early ages of onset has increased during the last decade, presumably because of improvements in renal imaging and consequent earlier age of diagnosis. In the current study, the mean age of diagnosis was estimated to be 20 years, with a standard deviation (SD) of 15.94. Under the best fitting model (autosomal dominant), over 70% penetrance was estimated by age 30 years, over 95% by 50 years, and 99% by 55 years. Thus, diagnosis of this disease at an early age is possible without total reliance on DNA typing. The segregation ratio defined through the transmission probability in our model was not significantly different from 0.50, but its confidence limits were broad: 0.36 to 0.64. Neither transmission probability nor penetrance was significantly influenced by gender. The mutation rate was estimated to be 6.9 x 10(-5), in accordance with the previously observed high mutation rate for PKD. However, the mutation rate in our study may be overestimated because it neglects low penetrance alleles and phenocopies.

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...