PREVENTION OF AORTIC FIBROSIS BY SPIRONOLACTONE IN SPONTANEOUSLY HYPERTENSIVE RATS

We have previously shown that long-term angiotensin-converting enzyme (ACE) inhibition prevents the increase in aortic collagen in spontaneo usly hypertensive rats (SHRs). independent of blood pressure reduction . More recently, we reported that the effects of ACE inhibition in the prevention of aortic collagen accumulation were related to the inhibi tion of angiotensin II actions on angiotensin II type 1 receptors. Ald osterone, the synthesis of which is mainly modulated by angiotensin II through type 1 receptor stimulation, is known to promote cardiac fibr osis in different experimental models. The aim of the present study wa s to determine whether inhibition of aldosterone formation was able to prevent aortic fibrosis in SHRs. For this purpose, we compared the ef fects of a 4-month treatment with the aldosterone antagonist spironola ctone with the ACE inhibitor quinapril in 4-week-old SHRs. Control SHR s and Wistar-Kyoto (WKY) rats received placebo for the same period of time. At the end of treatment, in conscious SHRs vs WKY controls, quin april completely prevented the development of hypertension, whereas sp ironolactone produced only a slight but significant reduction in blood pressure. Aortic hypertrophy was significantly prevented by ACE inhib ition but not by spironolactone. On the contrary, aortic collagen accu mulation was completely prevented by both quinapril and spironolactone . In the latter case, collagen density was significantly below that of WKY controls. These results show that in SHRs, spironolactone can mar kedly prevent aortic fibrosis in the presence of a very slight antihyp ertensive effect. It is suggested that ACE inhibition or type 1 recept or antagonist-induced prevention of aortic collagen accumulation is at least partially related to aldosterone inhibition.