P-443: Preliminary results of topiramate in an experimental model of obesity, insulin resistance and hypertension (obese Zucker rats)

Abstract

Epidemiological studies have shown the high association between obesity, type 2 diabetes mellitus, insulin resistance and hypertension. In this sense, pharmacological interventions tendent to body weight reduction induces amelioration of cardiovascular risk factors associated with obesity.

In the present ongoing work, we are testing the effects of Topiramate (TPM) (a neurotherapeutic agent currently indicated in the treatment of epilepsy and with described effects on body weight loss) on body weight reduction and its possible benefitial effect on an experimental metabolic cardiovascular syndrome (MCS).

For this purpose, we use a group of 45 obese Zucker rats (OZR). These animals develop the clinical features of the human metabolic CV syndrome with obesity, insulin resistance, dyslipidemia and hypertension.

Initially (at 4-5 weeks of age) animals were uninephrectomized in order to accelerate hypertension and organic cardiovascular damage. Then, animals were allocated to 3 groups according to the treatment. TPM-15 treated with 15 mg/day of Topiramate; TPM-60 treated with 60 mg/day of Topiramate and Control Group (CG) treated only with vehicle. Both, vehicle and TPM was administered by gavage.

At present moment, after 4 months of follow-up, some of the clinical and biochemical features are contained in the Table.

	BW (g)	PG (mg/dl)	TC (mg/dl)	TG (mg/dl)	SYST (mmHg)	DIAST (mmHg)	MAP (mmHg)
All animals (0 months)	297	102	141	130	144	106	117
	±30	±8.6	±8	±31	±13	±15	±15
CG (n = 15) (4 months)	623	104	504	2606	167	142	151
	±41	±8	±158	±1767	±1	±14	±14
TPM 15 (n = 15) (4 months)	597	93	415	1552	150	90	116
	±40	±9	±150	±1285	±12*	±32*	±25*
TPM 60 (n = 15) (4 months)	581	117	378	1433	153	95	113
	±40	±10	±117	±1133	±16*	±32*	±26*

BW: Body weight; PG: Plasma Glucose; TC: Total Cholesterol; TG: Tryglicerides; SYST: Systolic Pressure; DIAST: Diastolic Pressure; MAP: Mean Arterial Pressure

*

p<0.05 vs. CG

The present preliminary results appointed to a benefitial effect of TPM on the development of clinical damage in the present experimental model

Topiramate, Obesity, Hypertension

© American Journal of Hypertension, Ltd. 2002