Our research projects aim to study : - The regulation of the arterial blood pressure in women, in relationship with the segmental renal sodium handling and the renal hemodynamics. We investigate the influence of the endogenous and exogenous sex female hormones on the sodium sensitivity of the blood pressure and the renal hemodynamic response. Different physiologic situations as the luteal and follicular phases of the normal menstrual cycle , the menopause, the effects of the oral contraceptives have been characterized. The effects of the renin cascade blockade using angiotensin II receptors blockers on normotensive and hypertensive salt-repleted women are also analysed. - The pathophysiology of the systemic hypotension and its association with the renal segmental handling of sodium, and its potential damaging consequences on some ophthalmologic morbidities are also investigated. Our projets aim to investigate pathogenic mechanisms common for both the kidney and the eye. We have shown that women suffering from orthostatic hypotension had a renal nocturnal proximal wasting of sodium, this phenomenon aggravating the decrease of the systemic blood pressure. We also demonstrated that a high salt diet prevented orthostatic hypotension and associated symptoms. We now challenge the hypothesis that a dysregulation of the autonomous nervous system and other neuro-humoral cascades alters the renal sodium handling and favours systemic hypotension. This ultimately may be deleterious for the ocular perfusion and possibly the visual acuity, in certain ocular conditions as the normal pressure glaucoma. We plan to study the effect of a high salt diet and drugs on the preservation of the visual field in this particular condition. In certain families, normal pressure glaucoma and hypotension are highly prevalent, and we will analyse certain genetic polymorphisms associated with the renal sodium handling and the arterial blood pressure.
- The effects of the peroxisomal proliferator-activated receptor-gamma agonist pioglitazone on renal and hormonal responses to salt in healthy men. This study is conducted in a population of hypertensive patients and in subjects with diabetes type II, randomized to take pioglitazone vs. placebo, and pioglitazone vs. metformine respectively. The aim focuses on characterizing the occurrence of peripheral edema and the mechanisms triggering the sodium and water retention with these drugs. We perform a complete renal hemodynamic study, with the clearances of inulin and para-amino-hippurate, renal segmental sodium handling with the clearance of the endogenous lithium, the neuro-hormonal profile and the monitoring of the 24h ambulatory blood pressure, on both a low and a high salt diet for a 7 day period. - We are also working, in collaboration with the Services of Anesthesiology, HUG and of Nephrology, CHUV, Lausanne, the regulation of the arterial pressure in normal pregnancies and in pre-eclampsia. We plan to study the association between these conditions and certain variants of genes as CYP3A5 et ABCB1, eNOS, adrenergic receptors. Polymorphisms of these genes have been shown to be linked, in some hypertensive subgroups, with a high ambulatory blood pressure and with sodium sensitivity of the arterial pressure. - We are participating in an international multicentric controlled study on the effects of sulodexide on preventing the nephropathy in diabetic II patients with moderate renal failure and proteinuria