Effects of Ginkgo biloba extract (EGb 761) on the guinea pig vestibular system.

Previous studies have demonstrated that the administration of Ginkgo biloba extract (EGb 761) improves the compensation of the vestibular syndrome induced by transection of the VIIIth nerve. To investigate the mechanisms at play, the vestibular nuclei of alert guinea pigs were perfused with EGb 761. This perfusion always induced a stereotyped reversible postural syndrome that was the mirror image of the syndrome provoked by the unilateral lesion of the otolithical receptors. This result supports the hypothesis that EGb 761 has a direct excitatory effect on the lateral vestibular nuclei (LVN) neurons. In a second step, we quantified the horizontal vestibuloocular reflex (HVOR) of the normal guinea pig following IP injection of EGb 761. In normal guinea pig, IP administration of EGb 761 led to a reversible, dose-dependent decrease of the HVOR gain without affecting the phase of the reflex. These data help to explain the therapeutic effects of EGb 761 during vestibular syndromes and strongly suggest an impact at the neuronal level.

[Protective effect of cicletanine in hypertensive retinopathy. Evaluation of retinal function in the isolated retina]. / Effet protecteur du ciclétanine dans la rétinopathie hypertensive. Evaluation de la fonction rétinienne sur rétine isolée.

In order to demonstrate functional impairments related to hypertensive retinopathy, we experimented on the isolated retina of spontaneously hypertensive rats (SHR-SP strain A3N Iffa Credo). We also used this experimental model to assess the protective effect of treatment with cicletanine, a new synthetic furopyridine compound. Treatment consisted of daily oral administration of either 50 or 100 mg/kg of cicletanine for 5 weeks. Retinal function was evaluated by recording the electroretinogram (ERG) obtained in response to light stimulation (300 lux, 1 ms) of the isolated retina maintained in survival by perfusion. The results indicate: (i) that ERG amplitude remains systematically lower in hypertensive rats than in normotensive rats and that in consequence retina survival is shortened; (ii) that in cicletanine-treated hypertensive rats ERG amplitude is significantly higher than in untreated hypertensive rats, the drug augmenting the duration of retina survival. Although cicletanine significantly improved the ERG amplitude obtained in hypertensive rats, this amplitude was still lower than in normotensive rats. These results are consistent with those of previous histological studies performed on the same of hypertensive rats, which demonstrated that impairments of retinal capillaries, photoreceptors and ganglion cells may have deleterious functional consequences for the visual process. Cicletanine is able to reduce these histological impairments, and the present study demonstrate that the drug can also significantly improve the ERG amplitude.

Antihypertensive profile of cicletanine, a furopyridine derivative: comparison with captopril, indapamide and prazosin.

The effects of cicletanine were compared with those of three other antihypertensive drugs: prazosin, a highly selective alpha 1 antagonist, captopril an angiotensin converting enzyme inhibitor and indapamide a diuretic antihypertensive agent, on young stroke-prone SHR rats with high salt diet; furthermore, vascular reactivity to cicletanine was studied on isolated rat aorta. At an equal dose (30 mg/kg per os) all the drugs prevent the onset of hypertension with the same intensity. The minimal effective dose on blood pressure was 1 mg/kg for both cicletanine and captopril, and 3 mg/kg for indapamide. The action on diuresis and electrolyte excretion occurs at a dose of cicletanine 10 to 30 times higher than that required to produce the anti-hypertensive effect. One of the possible mechanisms of the antihypertensive effects of cicletanine could be due to a direct action of the drug on the vascular wall. This vascular impact could be an interaction with the alpha-adrenoceptor system (apparent pA2 cicletanine = 5.12) or a decrease in the vascular spasmogenic response whatever agonist was studied.

Comparison of cicletanine with other antihypertensive drugs in SHR-SP models.

The effects of cicletanine were compared with those of four other antihypertensive drugs (prazosin, a highly selective alpha 1 antagonist; captopril, an angiotensin-converting enzyme inhibitor; indapamide, an antihypertensive diuretic; and hydrochlorothiazide, a purely diuretic agent) on young stroke-prone SHR rats with high-salt diet. All the drugs except hydrochlorothiazide prevented the onset of hypertension. The minimal effective dose on blood pressure was 1 mg/kg for both cicletanine and captopril, and 3 mg/kg for indapamide. The action on cardiac hypertrophy and diuresis occurs at a dose of cicletanine 10 to 30 times higher than that required to produce the antihypertensive effect. Renal hypertrophy was also decreased significantly by cicletanine at a dose of 100 mg/kg.