Impaired Response to Insulin Associated with Protein Kinase C in Chronic Fructose-induced Hypertension

• Published in: Blood pressure Vol. 11; no. 6; pp. 345 - 351
• Main Authors: Damiano, P., Cavallero, S., Mayer, M., Rosón, M. I., Riva, I. de la, Fernández, B., Puyó, A. M.
• Format: Journal Article
• Language: English
• Published: Stockholm Informa UK Ltd 2002; Taylor & Francis
• Subjects: Animals; Arterial hypertension. Arterial hypotension; Atrial Natriuretic Factor - blood; Biological and medical sciences; Blood and lymphatic vessels; Blood Pressure - drug effects; Body Weight - drug effects; Cardiology. Vascular system; Enzyme Activators - pharmacology; Enzyme Inhibitors - pharmacology; Experimental diseases; Fructose; Fructose-FED Rats; Hypertension; Hypertension - chemically induced; Hypertension - enzymology; Hypertension - physiopathology; Hypoglycemic Agents - pharmacology; Insulin - pharmacology; Insulin Resistance; Insulin Resistance - physiology; Male; Medical sciences; Muscle Contraction - drug effects; Muscle, Smooth, Vascular - drug effects; Naphthalenes - pharmacology; Natriuretic Peptides; NG-Nitroarginine Methyl Ester - pharmacology; Nitric Oxide; Nitric Oxide - blood; Nitric Oxide - metabolism; Nitric Oxide Synthase - antagonists & inhibitors; Phorbol 12,13-Dibutyrate - pharmacology; Protein Kinase C - antagonists & inhibitors; Protein Kinase C - metabolism; Protein Kinases; Rats; Rats, Sprague-Dawley; Vascular Contractility; Hypertension; Protein kinase C; Rat; Enzyme; Pathogenesis; Transferases; Rodentia; Clinical form; Cardiovascular disease; Insulin; Fructose; Target tissue resistance; Vertebrata; Vasomotricity; Mammalia; Animal; Arterial pressure
• ISSN: 0803-7051; 1651-1999
• DOI: 10.1080/080370502321095302

A fructose-enriched diet induces an increase in blood pressure associated with metabolic alterations in rats. Our hypothesis was that an increase in protein kinase C (PKC) activation, reported in the acute period of fructose overload, and an impaired vessel's response to vasoactive substances contribute to maintain elevated blood pressure levels in the chronic period. The aims of this study were to investigate in this animal model of hypertension: (1) if the increase in PKC activation was also found in the chronic stage; (2) the involvement of nitric oxide and insulin in the vessel's response; and plasma atrial natriuretic factor and nitrites/nitrates (nitric oxide metabolites) behavior. We evaluated the effects of: PKCstimulator 12,13-phorbol dibutyrate, phenylephrine, insulin, nitric oxide synthase-inhibitor N G -nitro- L arginine methyl esther (L-NAME) and PKC-inhibitor Calphostin C on aortic rings responses of Sprague- Dawley rats: fructose-fed and control. The fructose-fed group showed higher contractility to 12,13- phorbol dibutyrate than the control group in aortic rings pre-incubated with insulin, and this difference disappeared with L-NAME. The response to phenylephrine in rings pre-incubated with Calphostin C was decreased in the fructose-fed group and increased with Calphostin C plus L-NAME. Fructose-fed rats showed higher levels of plasma atrial natriuretic factor and nitrites/nitrates than controls. In conclusion, chronic fructose feeding seems to develop an impaired response to insulin, dependent on nitric oxide, suggesting a PKC alteration. Vasorelaxant agents, such as atrial natriuretic factor and nitric oxide, would behave as compensatory mechanisms in response to high blood pressure.