These results show that PVAT enhances the arterial contractile response to perivascular nerve stimulation through the production of superoxide mediated by NAD(P)H oxidase, and that this enhancement involves activation of tyrosine kinase and MAPK/ERK pathway.

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The results indicate that both PMNs and brain microvessel endothelial cells possess AT1 receptor, that AT1 receptor antagonism ameliorates endothelial injury via inhibition of PMNs and endothelial cell adhesion, and that angiotensin II must be a key factor in hypertensive endothelial injury.

Abstract-The role of perivascular fat in the control of vascular function was studied using lipoatrophic A-ZIP/F1 transgenic mice. Only a small amount of brown fat was found around the aorta but not around mesenteric arteries. Blood pressure of A-ZIP/F1 mice became higher than wild-type (WT) mice from 10 weeks of age. The presence of perivascular fat reduced the contraction of WT aorta to phenylephrine and serotonin, whereas this effect was either absent or less prominent in A-ZIP/F1 aorta. In WT mice, transfer of solution incubated with aorta with fat to aorta with fat removed caused a relaxation response, but not in A-ZIP/F1 mice, indicating the release of a relaxation factor from perivascular fat in WT aorta. This factor was acting through the activation of calcium-dependent potassium channels. Perfusion of phenylephrine to the isolated mesenteric bed caused a higher increase in perfusion pressure in A-ZIP/F1 than in WT mice. O besity significantly increases the prevalence of associated risk factors, especially hypertension, and it is considered a major cardiovascular risk determinant, 1 but the mechanisms underlying the observed association between these diseases are poorly understood. It is now generally recognized that adipose tissue is an important endocrine and secretory organ, and some of its products, such as angiotensinogen (AGT), are important regulators of blood pressure. [2][3][4] In most systemic blood vessels, there is a layer of perivascular adipose tissue (PVAT) surrounding these vessels outside of the adventitial layer that may directly affect vessel wall structure and function. With the exception of the aorta, where there is usually a mixture of white and brown fat tissues, PVAT in most vessels is composed of white fat. It is now known that PVAT in the rat aorta secretes a vasodilatory substance that acts by a tyrosine kinase-dependent activation of K ϩ channels on the vascular smooth muscle cells, 5 an effect that we have now demonstrated in PVAT taken from a human thoracic artery. 6 We have recently developed a nongenetic model of adult obesity through fetal and postnatal exposure to nicotine, where we have found an increase in the amount of fat tissues in various parts of the body, including PVAT, but the PVAT from these obese animals did not cause vasodilation to the same degree as PVAT from the nonobese animals. 7 Taken together, these data suggest that altered function of PVAT may be a link between obesity and hypertension, but the mechanisms by which altered function of the PVAT may influence hypertension are currently not known.At the other end of the spectrum is lipoatrophy, where humans with a severe decrease in the amount of adipose tissue are known to suffer from insulin resistance, type 2 diabetes, and sometimes hypertension. 8 The A-ZIP/F1 mice were produced as a model for lipoatrophy study. 9 These transgenic mice have no white fat and a drastically reduced amount of brown fat. These mice are diabetic, with reduced leptin and elevated serum glucose, insulin, free fatty acid, an...