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Hypertension Overlaps with Insulin Resistance Mechanism

Animal study suggests hypertension triggers MMP activity that leads to proteolytic cleavage

WEDNESDAY, July 9 (HealthDay News) -- Hypertension may be the first step in the activation of matrix-degrading metalloproteinases and insulin receptor cleavage that leads to the development of insulin resistance, according to the results of an animal study published online July 7 in Hypertension.

Frank A. DeLano, of the University of California San Diego in La Jolla, Calif., and a colleague measured matrix metalloproteinase (MMP) activity in spontaneously hypertensive rats and normotensive control rats. They treated selected animals from both groups with doxycycline in drinking water for 24 weeks.

Compared to the control rats, the researchers found that the spontaneously hypertensive rats had higher levels of MMP in microvessels, mast cells and leukocytes, as well as cleavage by MMP-1,9 that co-localized with MMP-9 and was blocked by metal chelation. They also observed elevated protease activities in plasma and in microvascular endothelium associated with reduced density of extracellular binding domains of insulin receptors and CD18 membrane adhesion molecules. In spontaneously hypertensive rats, they found that doxycycline reduced protease activity in plasma and microvessels, blocked proteolytic cleavage of the insulin receptor, normalized blood glucose levels, and reduced blood pressure.

"Although the emphasis of the study is the insulin receptor, it is reasonable to suspect that many cell surface proteins could be vulnerable to damage and, consequently, disturbing regulation of endothelial and vascular muscle cell functions," states the author of an accompanying editorial. "This may lead to an understanding as to why there are so many different abnormalities associated with hypertension."

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