Hemodynamic and Metabolic Effects of Transdermal Clonidine in Patients With Hypertension and Non–Insulin-Dependent Diabetes Mellitus

Giugliano, Dario; Acampora, R; Marfella, Raffaele; Marca, C. La; Marfella, M. A.; Nappo, Francesco; D'Onofrio, F

doi:10.1016/s0895-7061(97)00319-1

Cited by 16 publications

(11 citation statements)

References 33 publications

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“…Our finding that clonidine treatment prevented the insulin resistance associated with weight gain in the dog is consistent with other reports. Giugliano et al 16 reported that in 20 hypertensive patients with non-insulin-dependent diabetes mellitus, clonidine treatment was associated with an improvement in insulin sensitivity in peripheral tissues. Using the glucose clamp, these investigators found that clonidine significantly improved overall glucose metabolism and that this improvement was accompanied by increases in both oxidative and nonoxidative glucose metabolism.…”

Section: Discussionmentioning

confidence: 99%

Clonidine Prevents Insulin Resistance and Hypertension in Obese Dogs

et al. 1999

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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...

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Section: Discussionmentioning

confidence: 99%

Clonidine Prevents Insulin Resistance and Hypertension in Obese Dogs

et al. 1999

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“…Transdermal clonidine has been successfully employed as adjunctive therapy with drug classes such as ACE inhibitors 16 and calcium channel blockers 17 ; however, when transdermal clonidine is provided as adjunctive therapy, it is unclear as to whether transdermal clonidine alone might have been sufficient for BP control 16 . Transdermal clonidine has also been shown to effectively reduce BP in hypertensive patients with type 2 diabetes while at the same time decreasing insulin resistance, microalbuminuria, and plasma fibrinogen 18 . In addition, clonidine (transdermal or oral) does not affect the cortisol response or the magnitude or rate of glucose recovery from insulin‐induced hypoglycemia 19 …”

Section: Blood Pressurementioning

confidence: 99%

Transdermal Clonidine: Therapeutic Considerations

Sica

Grubbs

2005

J of Clinical Hypertension

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“…96 A reflex increase in sympathetic tone in normotensive subjects can also lead to acute insulin resistance in the forearm. 97 Finally, clonidine, a drug that inhibits sympathetic outflow, improves insulin sensitivity in hypertensive patients with type 2 diabetes 98 and prevents insulin resistance in dogs fed a high-fat diet without affecting weight gain. 38 Whatever the mechanisms of insulin resistance, the cardiovascular consequences are serious: hyperinsulinemia and decreased vascular relaxation capabilities.…”

Section: Possible Mechanisms Of Obesity-induced Hypertensionmentioning

confidence: 99%

Pathways from obesity to hypertension: from the perspective of a vicious triangle

et al. 2002

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Obesity and arterial hypertension are important public health problems. Both overweight and hypertension predispose to cardiovascular diseases, such as myocardial infarction, stroke and renal failure. Moreover, overweight clearly predisposes to hypertension, and thus to an increased prevalence of cardiovascular diseases. This in turn favors inactivity and further weight gain, leading to an exacerbation of cardiovascular disorders. Obesity, hypertension and cardiovascular diseases thus contribute to three corners of a vicious triangle. It is within this conceptual framework that this paper reviews the pathogenesis of obesityrelated hypertension, which is highly complex. Many factors act together to promote vasoconstriction and sodium retention. Leptin, free fatty acids and insulin, whose levels are increased in obesity, may act synergistically to stimulate sympathetic activity and vasoconstriction. In addition, obesity-induced insulin resistance and endothelial dysfunction may operate as amplifiers of the vasoconstrictor response. Finally, increased renal tubular reabsorption of sodium may also occur, caused by an increased renal sympathetic nerve activity, the direct effect of insulin, hyperactivity of the renin -angiotensin system and possibly by an alteration of intrarenal physical forces. All together, these factors will lead to sustained hypertension. Because the prevalence of obesity was steadily increasing in the last decades, leading to an increased prevalence of hypertension and cardiovascular disorders, obesity and hypertension will most likely become the health challenges of the twenty-first century.

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Hemodynamic and Metabolic Effects of Transdermal Clonidine in Patients With Hypertension and Non–Insulin-Dependent Diabetes Mellitus

Cited by 16 publications

References 33 publications

Clonidine Prevents Insulin Resistance and Hypertension in Obese Dogs

Clonidine Prevents Insulin Resistance and Hypertension in Obese Dogs

Transdermal Clonidine: Therapeutic Considerations

Pathways from obesity to hypertension: from the perspective of a vicious triangle

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