Gertrud Schröder

Sexual dimorphism of blood pressure in spontaneously hypertensive rats: effects of anti-androgen treatment

The mechanisms resulting in the greater predisposition of male subjects towards hypertension were investigated in different strains of rats with genetic hypertension [spontaneously hypertensive rats of the stroke-prone strain (SHRSP) and spontaneously hypertensive rats (SHR)] and their respective normotensive controls. Blood pressure was reduced in young (9 weeks of age) hypertensive rats by (1) surgical castration, (2) treatment with the testosterone receptor antagonist cyproterone acetate (CPA), which does not elevate testosterone, or (3) with the testosterone receptor antagonist flutamide, which leads to a feedback elevation of gonadotrophic hormones and plasma testosterone. These treatments had no effect on high blood pressure in old hypertensive rats aged 25 weeks. Both androgen receptor antagonists attenuated high blood pressure development when given for the first 10 days after birth. These data clearly relate the sexual dimorphism of hypertension to testosterone produced during male brain maturation in the early phase of hypertension development. Testosterone appears not to contribute directly to the maintenance of high blood pressure in established hypertension.

Comparison of the Effects of Calcipotriol, Prednicarbate and Clobetasol 17-Propionate on Normal Skin Assessed by Ultrasound Measurement of Skin Thickness

In this study, we investigated the effect of calcipotriol, prednicarbate and clobetasol 17-propionate on skin thickness over a treatment period of 6 weeks. The study was conducted as a controlled, randomized, double-blind comparison. The influence of these drugs on normal skin under occlusive conditions was assessed visually and by measuring skin thickness using 20 MHz B mode ultrasound. Both topically applied glucocorticosteroids lead to a significant decrease in skin thickness. In contrast to the glucocorticosteroid-induced atrophy, calcipotriol application on normal skin leads to an increase in skin thickness in all volunteers. The effect remains constant for the duration of treatment. The cause of this increase seems to be an irritative reaction of the skin which was histologically investigated in one volunteer. The histological features of this reaction are characteristic for a subacute dermatitis. The implications of these findings for the therapeutic mechanism of calcipotriol are discussed.

Contribution of serotonergic systems to maintenance of blood pressure in anaesthetised normotensive Wistar Kyoto and conscious spontaneously hypertensive rats.

Recent investigations clearly indicate a contribution of central serotonergic neurons to the regulation of arterial pressure (Kuhn et al. 1980). However, the mode of interaction between serotonergic pathways and central sympathetic networks and their effect on blood pressure is still unclear. In the midbrain, electrical stimulation of serotonergic neurons in the raphe nuclei activates sympathetic nerve discharge and thereby increases blood pressure (McCall & Harris 1987). Stimulation of more caudally located 5-HT neurons (raphe pallidus, raphe magnus and raphe obscurus), from which sympathoexcitatory and sympathoinhibitory pathways descending to the spinal cord originate, leads to an increase as well as a decrease in blood pressure. The sympathoexcitatory effect of electrically stimulated serotonergic neurons in the raphe nuclei can be blocked by methysergide or metergoline, whereas sympathoinhibitory effects remain unaffected by these agents, indicating the involvement of different serotonin receptors (McCall & Humphrey 1982). Exogenous serotonin injected into the lateral ventricle gave species-dependent results with blood pressure increases in rats and decreases in cats and dogs (Krstic & Djurkovic 1976). Little information is available on the contribution of serotonergic neurons in the pathogenesis of essential hypertension. In young prehypertensive spontaneously hypertensive rats (SHR) an increased serotonin turnover in different brain stem nuclei has been observed (Koulu et al. 1986). In the present study the contribution of serotonergic neurons to blood pressure regulation was tested in conscious SHR and anaesthetised normotensive Wi star rats by use of ZK 33839, an antagonist at both serotonergic S2and ai-adrenergic receptors.