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)
Küng
C F
CF
Department of Research, University Hospital, Basel, Switzerland.
Lüscher
T F
TF
D000375:Aging / Q000502:physiology*; D000818:Animals; D001011:Aorta / Q000503:physiopathology*; D001794:Blood Pressure; D001835:Body Weight; D016232:Endothelins / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014661:Vasoconstriction / Q000502:physiology; D014664:Vasodilation / Q000502:physiology
D016232:Endothelins; D011189:Potassium Chloride