Effect of Castration and Testosterone Substitution on the Urinary Output of Gamma-Glutamyl Transpeptidase and of N-Acetyl-Beta-D-GIucosaminidase of Male Rats with Renovascular Hypertension

Abstract

The effect of castration of male rats with experimental renal hypertension (‘two kidney Goldblatt hypertension’) was studied on the height of the hypertension and on the urinary output of γ-glutamyl transpeptidase (γGT) and of N-acetyl-beta-D-glucosaminidase (NAG). Castration was carried out immediately after clamping one renal artery. Some of the castrates received testosterone substitution from the 3rd postoperative week onwards. Uncastrated hypertensive males served as controls. The experiments were carried out 8-18 weeks after eliciting high blood pressure. Hypertension as well as enzymuria were less expressed in castrates than in uncastrated males or in testosterone-substituted rats. In all animals studied the γGT excretion rate showed a positive correlation with the blood pressure. The output of γGT and of NAG as well as the specific γGT activity of the renal membrane fraction was lower in castrates than in uncastrated males or in substituted castrates. In uncastrated males and in testosterone-substituted castrates the daily NAG output showed a direct correlation with the renal hydroxyproline content. No such correlation was found in castrated males. The kidneys of castrates and of testosterone-substituted castrates contained less hydroxyproline than those of uncastrated males.

Urinary Output Modulation of Alanine Aminopeptidase, γ-Glutamyl Transpeptidase and N-Acetyl-ß-D-Glucosaminidase by Castration and Testosterone in Male Normal Rat

“…It seems that mais, but obviously renovascular hyperten-testosterone is implicated in the time-depension could interfere with enzymuria as re-dent increase of urinary AAP and y-GT obported for other renal enzymes such as kalli-served under normal growth development in krein [11,12]. In spite of these differences of male rats, protocol, our results are consistent with the study of Malyuz and Ehrens [8] regarding the effect of castration and testosterone on uri nary excretion of y-GT.…”

“…To our knowledge only one study [8] has investigated the influence of castration and testosterone administration on the urinary excretion of brush border proximal tubular enzymes (in that case only NAG and y-GT). However, the experiment was conducted in 'two kidney-one clip Goldblatt hyperten sion'.…”

“…However, NAG is a lysosomal enzyme whose output is related to the renal hydroxyproline content and thus may be associated with the devel opment of nephrosclerosis [8], The develop ment of nephrosclerosis had been reported in the early stage of 'two kidney-one clip hypertension' [9,10]. It is therefore possible to explain the discrepancies between our study and this previous report [8] in the tes tosterone effects on the output of NAG by the morphological changes of renal tissue induced by the hypertensive state. Another interesting observation is the time delay in the development of the difference between sham control and castrated rats.…”

Androgen receptor (AR) in cardiovascular diseases

“…They found that the surgical and chemical castrations in these males reduced blood pressure levels down to the similar levels as observed in females (Reckelhoff, Zhang et al 1999). Similar results were reported in other castrated animal models (Malyusz and Ehrens 1983; Malyusz, Ehrens et al 1985; Woods, Morgan et al 2010). In addition, Ely et al found that the Tfm rat, lacking functional AR, and castrated rats have lower blood pressure than intact control rats (Ely, Salisbury et al 1991), suggesting that androgen/AR signaling might be involved in hypertension.…”

A comparison of the development of renal hypertension in male and female rats

“…The finding that the success rate of inducing renal hypertension in females was increased dramatically by prior ovariectomy, points to an influence of endogenous ovarian hormones on the development of hypertension in this model. Indeed, gonadal hormones have been reported to influence the onset and severity of hypertension in other hypertensive models [1,2,[20][21][22][23]. Although plasma hormonal levels were not measured in the present study, on completion of the study, the absence of ovarian tissue was confirmed and vaginal smears taken from the ovariectomized rats were similar to those obtained at stages of the oestrous cycle when levels of both oestradiol and progesterone are low [24].…”