| This dissertation examines hypertension in two animal models. The first will examine the effects of a high fat (HF)-diet in juvenile rats. The second part will examine the effects of treating rats with mineralocorticoid induced hypertension with pentoxifylline (PTX), a phosphodiesterase inhibitor with anti-inflammatory properties.; In the United States, children are becoming obese at an alarming rate, yet the cardiovascular effects of juvenile obesity have not been studied. It has been shown that obesity and hypertension have a strong correlation. Increases in vasoconstriction and decreased vasodilation also occur in hypertension and may result in the maintenance of high blood pressure. Therefore we hypothesized that feeding young rats a HF-diet would result in the development of hypertension and increased alpha-adrenergic activity.; To test this hypothesis we fed 3-week old male Sprague-Dawley rats a HF-diet for 10 weeks. At the end of the 10 weeks the rats were hypertensive, had increased oxidative stress and the maximum constriction in the aorta to alpha-adrenergic stimulation was increased compared to control. Surprisingly, this occurred without an increase in activity of the renin-angiotensin-aldosterone system.; Three cyclooxygenase (COX) enzymes (1, 2 and 3) can metabolize arachidonic acid (AA) into vasoactive prostanoids and their expression is altered in hypertensive animal models. To further examine vascular responses in young rats fed a HF-diet, vascular reactivity to AA was measured in the aorta. Augmented AA-induced vasoconstriction was seen in the rats fed a HF-diet, compared to control. This response seems to be mediated by increased expression and activity of COX 1.; The second part of this dissertation examines the role of inflammatory cytokines in mineralocorticoid-induced hypertension. We hypothesized that treating deoxycorticosterone-acetate salt (DOCA) rats with PTX, would decrease blood pressure and end organ damage by decreasing oxidative stress and inflammation. Treating DOCA rats with PTX resulted in decreased cardiac hypertrophy, decreased oxidative stress and decreased kidney damage. Plasma levels of monocyte chemoattractant protein-1, an inflammatory cytokine, were reduced suggesting PTX did reduce the inflammatory response.; The results of these studies provide greater insight into the pathogenesis of juvenile obesity induced hypertension and mineralocorticoid induced hypertension. |
