Different mechanisms of endothelial dysfunction with aging and hypertension in rat aorta

We analyzed the effects and mechanisms of aging in aortic endothelium and vascular smooth muscle of 12-week-old (adult) and 72-week-old (senescent) normotensive Wistar-Kyoto rats (WKY) and spontaneously hypertensive rats (SHR). Aortas were suspended in organ chambers filled with physiological salt solution (95% O2/5% CO2; 37 degrees C), and isometric tension was measured. In WKY, endothelium-dependent relaxations to acetylcholine were diminished with aging (P < .05); in SHR, they were reduced compared with WKY (P < .05) but unchanged with aging. The thromboxane/endoperoxide receptor antagonist SQ 30741 increased relaxations only in adult SHR. Relaxations to sodium nitroprusside were slightly enhanced with age in WKY and SHR (P < .05). Endothelium-dependent contractions to acetylcholine were unmasked by NG-nitro-L-arginine methyl ester (P < .05) and prevented by SQ 30741 or endothelium removal. In WKY, contractions increased with age. In adult SHR, marked endothelium-dependent contractions occurred (P < .05 versus WKY), which diminished with age (P = NS versus senescent WKY). The thromboxane analogue U46619 elicited similar contractions in adult and senescent WKY and adult SHR, whereas responses in senescent SHR were weaker (P < .05). In WKY and SHR, contractions to norepinephrine were similar and unaltered by aging. In WKY, contractions to endothelin-1 remained unaffected by aging. Adult SHR exhibited contractions to endothelin-1 comparable to those in WKY, whereas senescent SHR contracted less (P < .05). Bosentan, a combined endothelin-A/endothelin-B receptor antagonist, inhibited endothelin-1 markedly, especially in SHR (P < .05).(ABSTRACT TRUNCATED AT 250 WORDS)