Changes in aortic levels of tropoelastin mRNA following treatment of rats with the antihypertensive drugs captopril and hydralazine.
This manuscript describes changes in the steady state levels of aortic tropoelastin mRNA in spontaneously hypertensive rats (SHR) and normotensive controls (WKY) following treatment with two antihypertensive drugs. Three-week-old WKY and SHR rats were treated with hydralazine (15 mg/kg/day) or captopril (25 mg/kg/day). Tail artery blood pressure was monitored twice weekly. Both drugs prevented the development of hypertension in the SHR rat. At 6 weeks of age, total aortic RNA was extracted and the steady state levels of mRNAs coding for tropoelastin and pro alpha 1 (III) collagen were determined by slot blot hybridization analysis using radiolabeled tropoelastin and pro alpha 1 (III) collagen cDNA clones. Hydralazine treatment resulted in a threefold increase in tropoelastin mRNA levels in both the SHR and the WKY animals (P less than 0.01). Captopril-treated SHR animals demonstrated a similar significant increase. In contrast, no differences in pro alpha 1 (III) collagen mRNA levels were observed in the aorta of SHR or WKY rats following treatment with either captopril or hydralazine. These data suggest that antihypertensive agents can act specifically to directly induce tropoelastin mRNA levels in large arteries and thus may induce vascular remodeling independent of an increase in blood pressure.
Department of Surgery, UMDNJ-Robert Wood Johnson Medical School, New Brunswick 08903.
S M
SM
Alden
R A
RA
Pierce
C A
CA
Tozzi
J W
JW
Mackenzie
S B
SB
Deak
C D
CD
Boyd
D000375:Aging / Q000502:physiology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000378:metabolism*; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology*; D006830:Hydralazine / Q000494:pharmacology*; D009693:Nucleic Acid Hybridization; D012333:RNA, Messenger / Q000378:metabolism*; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014333:Tropoelastin / Q000235:genetics*
D000959:Antihypertensive Agents; D012333:RNA, Messenger; D014333:Tropoelastin; D006830:Hydralazine; D002216:Captopril