Date of Award
Doctor of Philosophy (PhD)
Dr. R.M.K.W. Lee
In spontaneously hypertensive rats (SHR), treatment with the arterial vasodilator minoxidil does not prevent or attenuate the progression of cardiovascular hypertrophy despite blood pressure control, and the reason is generally unknown. The purpose of this study, was to examine temporal changes of cardiac and mesenteric arterial structure with respect to changes in volume load and cardiac and arterial sympathetic activity, during chronic treatment of normotensive and SHR with minoxidil alone, or in combination with the diuretic hydrochlorothiazide (HCTZ). The hypothesis to be tested is that an increase in the sympathetic activity and/or cardiac and intravascular volume is involved in causing these structural changes. In normotensive rats, minoxidil induced (i) right ventricular hypertrophy (RVH), (ii) eccentric left ventricular hypertrophy (LVH), (iii) medial hypertrophy of the superior mesenteric artery, (iv) intravascular volume expansion, (v) increases in cardiac filling pressures, (vi) increases in ventricular and arterial norepinephrine turnover rates. In SHR, minoxidil (i) decreased blood pressure, (ii) potentiated RVH, (iii) caused the development of eccentric LVH superimposed on the preexisting hypertrophy, (iv) increased the lumen of the superior mesenteric artery, (v) prevented further increases in medial hypertrophy of the large and small mesenteric arteries, (vi) induced intravascular volume expansion, (vii) increased ventricular but decreased arterial norepinephrine turnover rates, and (viii) increased elastin content and decreased elastase activity in the large conducting vessels (aorta, superior mesenteric artery). In SHR and normotensive rats, concomitant diuretic treatment prevented intravascular volume expansion, caused concentric LVH rather than eccentric LVH and no longer increased the medial and luminal areas of the superior mesenteric artery. These results suggest that there are regional differences in the response of the cardiovascular system to minoxidil in SHR and normotensive rats. Some of these differences may relate to differences in regional sympathetic activity, whereas volume load appears to play a modulatory role.
Tsoporis, Jim, "Effects of arterial vasodilators on cardiovascular hypertrophy and sympathetic activity in normotensive Wistar and spontaneously hypertensive rats" (1999). Open Access Dissertations and Theses. Paper 1799.