Abstract-The role that the central sympathetic nervous system plays in the development of obesity hypertension and insulin was evaluated by feeding dogs a high fat diet with or without clonidine treatment. Thirteen adult mongrel dogs were chronically instrumented and randomly assigned to receive either a high fat diet and no clonidine (nϭ6) or a high fat diet plus clonidine (nϭ7), 0.3 mg BID. Blood pressure, heart rate, plasma insulin, and electrolytes were measured daily. Insulin resistance was assessed with a multiple-dose euglycemic clamp (1, 2, and 30 mU ⅐ kg Ϫ1 ⅐ min Ϫ1 ) before and after 1, 3, and 6 weeks of the high fat diet. Clonidine prevented the hypertension, tachycardia, and insulin resistance associated with feeding dogs the high fat diet but did not affect weight gain. The present study suggests that the central sympathetic nervous system plays a critical role in the development of both insulin resistance and hypertension associated with feeding dogs a high fat diet. Key Words Ⅲ hypertension, arterial Ⅲ obesity Ⅲ insulin resistance Ⅲ clonidine Ⅲ sympathetic nervous system Ⅲ cardiac output T he mechanism involved in the pathogenesis of the increased blood pressure in obesity is incompletely understood. Studies in our laboratory 1,2 and by others 3 suggest that insulin resistance may be the link between obesity and hypertension. However, other observations suggest that the relation between insulin and obesity-induced hypertension is not so straightforward. The San Antonio Heart Study showed that hyperinsulinemia is more common in Mexican Americans than in white non-Hispanics, yet the prevalence of hypertension is high in the latter group. 4 Hall et al 5 failed to observe an increase in blood pressure when normal dogs were given a chronic infusion of insulin with or without norepinephrine.We believe that an alternate hypothesis to explain the pathogenesis of obesity-induced hypertension is that chronic central sympathetic nervous system activation links insulin resistance and hypertension. Sowers et al 6 observed that borderline hypertensive obese subjects had higher norepinephrine levels than did nonobese normotensive control subjects, that their blood pressure correlated with norepinephrine levels, and that weight loss was accompanied by a fall in blood pressure that correlated with a decrease in serum norepinephrine. Hall et al 7 suggested that combined ␣-and ␤-adrenergic blockade reduced arterial pressure to a much greater extent in obese than in normal dogs. Fasting or caloric deprivation reduces sympathetic activity and overfeeding stimulates sympathetic activity. 8 Diebert and DeFronzo 9 demonstrated that impairs both peripheral and hepatic resistance to the action of insulin.Jamerson et al 10 demonstrated that a reflex increase in sympathetic tone in normotensive individuals can lead to acute insulin resistance in the forearm.Thus, it is possible that central activation of the sympathetic nervous system is the physiological link that connects excess dietary intake to insulin resistance and hyp...

Objective: The introduction of atypical antipsychotics was a big step forward in the treatment of schizophrenia and other psychoses. However, they are liable to cause weight gain and hence further put the patient at risk of metabolic disorders. Our aim was to evaluate the weight gain associated with the use of olanzapine, in relation to age and gender, in patients of Schizophrenia.One hundred patients fulfilling the ICD-10 criteria for Materials and methods: schizophrenia, were included in this study to evaluate weight gain as an adverse effect of treatment with olanzapine in relation to age, gender, dose and body mass index (BMI). Sociodemographic data and baseline weight along with height (to calculate the BMI) were recorded before the initiation of treatment. The patients were administered a flexible dose of olanzapine (5-15 mg) as monotherapy. Pregnant patients, smokers, patients with history of endocrine disorders, CVS disease and chronic alcoholics were excluded from the study. The increase in weight as a neuroleptic side-effect of olanzapine was recorded and analysed in relation to age, gender, dose and BMI. Observations and results: Of the patients receiving olanzapine, 66.6% had a weight gain of 1-5 kg over a period of 4 weeks. The weight gain was not related to the dose of the drug or BMI. The increase in weight was significantly related to age 45 years and ≥ female sex, indicating that women 45 years of age are more prone to gain weight with olanzapine therapy in ≥ comparison with women <45 years and men of any age group.The potential for weight gain associated Conclusion: with the use of olanzapine is high in females more than 45 years of age. The potential of olanzapine to cause long-term complications will need further study.