Conceptual basis and methodology of the SOPHIA study.

To clarify the role of gene polymorphisms on the effect of losartan and losartan plus hydrochlorothiazide on blood pressure (primary end point) and on cardiac, vascular and metabolic phenotypes (secondary end point) after 4, 8, 12, 16 and 48 weeks treatment, an Italian collaborative study - The Study of the Pharmacogenomics in Italian hypertensive patients treated with the Angiotensin receptor blocker losartan (SOPHIA) - on never-treated essential hypertensives (n = 800) was planned. After an 8 week run-in, losartan 50 mg once daily will be given and doubled to 100 mg at week +4 if blood pressure is more than 140/90 mmHg. Hydroclorothiazide 25 mg once daily at week +8 and amlodipine 5 mg at week +16 will be added if blood pressure is more than 140/90 mmHg.

Fetal ontogeny and role of metanephric bradykinin B2 receptors.

Previous studies in rats have shown that blockade of bradykinin B2 receptors (B2R) in combination with a high-salt intake during gestation result in poor postnatal survival and long-term hypertension in the offspring. In this study, we examined the fetal ontogeny of B2R and determined the consequences of gestational B2R blockade and high salt on kidney development. B2R gene expression is induced on embryonic day (E16) of fetal metanephrogenesis and remains sustained until term.

High plasma prorenin in non diabetic siblings of non insulin-dependent diabetes mellitus patients.

In a large cohort (no. = 361) of NIDDM probands and their concordant/discordant siblings from no. = 132 families we studied: 1.

Blood pressure sensitivity to salt in rats with low urinary kallikrein excretion.

We evaluated if a rat strain inbred for reduced urinary kallikrein excretion differs from normal-kallikrein Wistar rats regarding blood pressure in basal conditions and during alterations in sodium balance. Low-kallikrein rats showed greater systolic blood pressure values (125 +/- 3 vs. 114 +/- 2 mmHg in controls, P < 0.

Urinary kallikrein: a marker of blood pressure sensitivity to salt.

We evaluated if a rat strain inbred for low urinary kallikrein excretion differs from normal-kallikrein Wistar rats regarding blood pressure levels in basal conditions and during alterations in sodium balance. Blood pressure was measured in unanesthetized rats on normal sodium intake. Then, blood pressure sensitivity to salt was evaluated over a period of 20 days of high sodium diet (0.

Sexual dimorphism of cardiovascular responses to early blockade of bradykinin receptors.

To assess whether the cardiovascular effects induced by early blockade of bradykinin B2-receptors with Hoe 140 (D-Arg[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin) are influenced by sex, Wistar rats of both sexes received the antagonist (300 nmol/d per kilogram body wt) or vehicle from 2 days to 7 weeks of age by subcutaneous injection and then by intraperitoneal infusion. Compared with control rats, Hoe 140-treated female rats showed higher systolic blood pressure levels at 7 and 9 weeks of age (125 +/- 2 versus 111 +/- 2 mm Hg and 132 +/- 3 versus 116 +/- 2 mm Hg, respectively, P < .05), whereas in male rats a difference was found at 7 weeks (122 +/- 4 versus 108 +/- 4 mm Hg, P < .

Recognition of markers of response to potassium-canrenoate in essential hypertension.

Potassium canrenoate (K-Can) prevents hypertension in Milan hypertensive strain (MHS) but not in spontaneously hypertensive rats (SHR). Essential hypertensive patients (HT) may have differential sensitivity to diuretics, since a subgroup of HT insensitive to hydrochlorothiazide (HCTZ) but sensitive to K-Can has previously been found. The aims of this study were: 1) to seek markers of response in essential hypertensive patients selectively sensitive to K-Can: and 2) to test whether selective sensitivity to furosemide may also be demonstrated.

Chronic inhibition of bradykinin receptors alters cardiovascular function in rats with an excess of circulating vasoconstrictors.

1. The contribution of endogenous kinins to the regulation of blood pressure of angiotensin-treated rats was evaluated using the new bradykinin B2-receptor antagonist Hoe 140 (D-Arg[Hyp3,Thi5,D-Tic7,Oic8]-bradykinin). 2.

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.

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.

[Protective effect of a calcium antagonist against renal vasoconstriction induced by endothelin in the normotensive rat].

We studied the effect of nifedipine, a dihydropyridine calcium antagonist, on the hemodynamic changes induced by endothelin, in awake normotensive rats. Endothelin (0.07-1.

[Effect of chronic enalapril treatment on prorenin, renin and sex hormones during the menstrual cycle in patients with essential hypertension].

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].

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.