The role of angiotensin II on vascular hypertrophy in genetic and renovascular hypertension
thesisposted on 15.12.2014, 10:29 by Helen J. Fish
Angiotensin II, generated either within the circulation, or within the vasculature has been suggested to have trophic effects on the vasculature. The present studies were designed to separate pressure-dependent effects on vascular structure from pressure-independent trophic effects of angiotensin II, in two experimental models of hypertension. Spontaneously hypertensive rats were treated from three to twenty four weeks of age with the angiotensin-converting enzyme inhibitor perindopril. In addition, ACE inhibitor treatment was given in the presence of elevated dietary salt intake. This was found to attenuate the antihypertensive effects of perindopril and similar blood pressure-related structural alterations were observed, compared to the untreated SHR, in spite of the absence of Angiotensin II.;Goldblatt one-kidney, one clip rats were treated for either four, or eight weeks post clipping with either the ACE inhibitor perindopril, or the angiotensin II receptor antagonist losartan. Renin-angiotensin system blockade failed to prevent the development of hypertension in the one-kidney, one-clip rats, thus allowing specific effects of angiotensin II on vascular structure to be dissociated from those related to a reduction in blood pressure. Only slight alterations in vascular structure were observed in the absence of a reduction in blood pressure.;Overall, these results suggest that blood pressure elevation is a major determinant of structural vascular change. There was little evidence of a major direct angiotensin II mediated trophic effect, although slight effects of the renin-angiotensin system could not be ruled out. Endothelial dysfunction in these models also largely appeared to develop as a consequence of blood pressure elevation, although some improvement in endothelial function was observed as a result of drug treatment.