Effect of chronic intracerebroventricular dexamethasone on blood pressure in normotensive rats.

We report herein the effects of long-term intracerebroventricular (icv) dexamethasone in normotensive rats. Dexamethasone (0.002, 0.02, 0.2, and 2.0 micrograms/day) or its vehicle (0 microgram/day, n = 8 each group) was infused icv via subcutaneous miniosmotic pumps (Alzet 2002) for 24 days in male conscious Wistar rats (weight range 190-240 g). Eighteen Wistar rats (weight range 200-230 g) received either vehicle or dexamethasone (0.2 and 2 micrograms/day) subcutaneously (sc) for 24 days. Systolic blood pressure (SBP, tail cuff) and body weight were recorded two times a week in the trained conscious rats. Dexamethasone (0.2 micrograms/day icv) exerted a progressive significant decrease in SBP over 24 days compared with both rats receiving vehicle and to pretreatment values (108 +/- 4 vs. 122 +/- 4 and 120 +/- 2 mmHg, P < 0.01). As previously reported, a significant increase in SBP was observed after 6 days in rats given 2 micrograms/day sc dexamethasone compared with both rats receiving vehicle and to pretreatment values (150 +/- 4 vs. 122 +/- 2 and 120 +/- 2 mmHg, P < 0.01 for both). Thereafter, SBP remained at plateau for the entire experiment. A similar significant decrease in body weight gain with age was observed in rats given icv or sc dexamethasone. Our data suggest that the glucocorticoid receptors exert opposite effects on blood pressure when stimulated at the brain level instead of at the peripheral vascular level.

Kinin antagonist blunts the diuretic effect of furosemide in deoxycorticosterone-treated rats.

Furosemide at a dose of 3 mg/kg body wt increased urinary volume (vehicle: 12.8 +/- 0.6; furosemide: 42.4 +/- 2.6 ml/8h, p < 0.01) and urinary sodium excretion (vehicle: 0.9 +/- 0.1; furosemide: 5.0 +/- 0.4 mM/8h, p < 0.01) in deoxycorticosterone-treated rats. These effects were associated to a decrease in mean blood pressure (from 122 +/- 4 to 113 +/- 3 mmHg, p < 0.01) and renal vascular resistances (from 15.6 +/- 0.6 to 14.3 +/- 0.7 RU, p < 0.05). The B2-receptor antagonist D-Arg[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin significantly blunted the diuretic and natriuretic effect of furosemide and completely prevented the decrease in blood pressure and renal vascular resistances. The renal kallikrein-kinin system may modulate the diuretic and hemodynamic effects of furosemide in conditions of increased mineralcorticoid activity.

Prorenin is present in human red blood cells.

We looked for the presence of prorenin in erythrocytes from normal subjects (n = 8), hypertensive patients (n = 8), and pregnant women (n = 8). Angiotensin I generation was measured at 37 degrees C, pH 5.7, in the presence of homologous substrate (1400 ng/mL) before and after trypsin activation (100 micrograms/mL) in (A) haemolyzed erythrocytes, (B) supernatants of haemolyzed erythrocytes, and (C) in the sixth washing of erythrocytes diluted 1:1 with a 0.1 M Tris buffer containing 0.5% bovine serum albumin and protease inhibitors. Haemolyzed erythrocytes generated angiotensin I only after trypsin treatment, and the rate of generation was the same (A) before and (B) after centrifugation at 20,000g, indicating the absence of prorenin bound to the cell membranes. When aliquots of the last washing of erythrocytes (C) were tested for angiotensin I generation before and after trypsin, they did not generate angiotensin I, indicating that residual prorenin from the plasma was no longer present in our preparation. Angiotensin I generation by trypsin-treated A and B was completely abolished by preincubation with anti-renin serum. The level of prorenin was not significantly different in the erythrocytes from normal, hypertensive, and pregnant subjects (68 +/- 10, 58 +/- 7 and 107 +/- 17 pg angiotensin I.mL-1.h-1, ns) in spite of their very different plasma levels (21 +/- 2.5, 17 +/- 2.4 and 110 +/- 12 ng angiotensin I.mL-1.h-1, p less than 0.01 for pregnant women compared with both normal and hypertensive subjects). Our data show that prorenin is present in human erythrocytes in fairly constant and clearly detectable amounts, thus suggesting a possible intracellular role for it.

Depressed urinary excretion of epidermal growth factor in psoriasis.

Epidermal growth factor (EGF) may have a modulatory role in renal growth and function. The aim of the present study was to evaluate whether urinary excretion of EGF is altered in psoriatic patients with or without arterial hypertension. The glomerular filtration rate was similar in psoriatics as compared with age- and sex-matched controls, whereas urinary EGF (microgram/g creatinine) was significantly reduced in psoriatics: normotensive subjects, 29.52 +/- 3.51 (psoriatics) versus 44.31 +/- 1.20 (controls, p less than 0.05); hypertensive subjects, 19.67 +/- 3.96 (psoriatics) versus 30.11 +/- 1.52 (controls, p less than 0.05). The urinary EGF excretion was lower in males than in females, save for hypertensive psoriatics. Urinary EGF correlated inversely with age and directly with urinary kallikrein excretion. Urinary kallikrein activity was reduced and microalbuminuria increased in hypertensive psoriatics. These alterations might suggest that initial deterioration of renal function is present in psoriasis.

[Effect of chronic enalapril treatment on prorenin, renin and sex hormones during the menstrual cycle in patients with essential hypertension]. / Effetti del trattamento cronico con enalapril su prorenina, renina ed ormoni sessuali durante il ciclo mestruale in pazienti ipertese essenziali.

Since angiotensin II seems to be involved in the process of ovulation we studied the effect of chronic enalapril on plasma prorenin, renin, estradiol, progesterone, LH and FSH during the menstrual cycle in ten essential hypertensive women. Our data show that peripheral blockade of A I conversion does not affect the pituitary guidance and the ovarian hormonal response of the menstrual cycle and, we can speculate, that it does not interfere with the process of ovulation.

[Effect of menstrual cycle hormones on cation transport in the red-cell membrane]. / Influenze degli ormoni del ciclo mestruale sui trasporti cationici di membrana dei globuli rossi.

Erythrocyte cation transport, plasma prorenin and renin and sexual hormones were sequentially evaluated in 12 normal volunteers over the menstrual cycle. Na-K cotransport and Na-Li countertransport raised in 6 out of 12 subjects in synchronization with the ovulatory phase. When the maximal % variation (ovulatory phase) versus baseline (follicular phase) of the Na-K cotransport was plotted versus the maximal % increment of oestrogens. A direct, highly significant inverse correlation was observed (r = 0.904, p less than 0.001). Moreover, a highly significant inverse correlation between plasma prorenin and intraerythrocyte Na (r = -0.857, p less than 0.001) in the follicular phase was found. Our data suggest that erythrocyte cation transport can be influenced by sexual hormones in human.