Effect of aging and hypertension on contractility of resistance arteries: modulation by endothelial factors.
The effects of aging and hypertension on contraction were examined in rat mesenteric resistance arteries of 12- and 74-wk-old Wistar-Kyoto (WKY) and spontaneously hypertensive rats (SHR). The vessels were suspended in myographs (37 degrees C, 95% O2-5% CO2) filled with modified Krebs-Ringer bicarbonate solution. Isometric tension was measured. Contractions to KCl (100 mM) were similar in adult WKY and SHR; they increased in senescent WKY (P < 0.05) but decreased in senescent SHR (P < 0.05). Responses to norepinephrine (% of KCl) were comparable in all four groups. However, blockade of nitric oxide (NO) production with NG-nitro-L-arginine methyl ester (L-NAME) enhanced the sensitivity to norepinephrine in senescent animals, particularly in SHR. Inhibition of cyclooxygenase with indomethacin prevented increased sensitivity to norepinephrine after NO blockade. Responses to angiotensin (ANG) II were not affected by aging and hypertension, but the thromboxane receptor antagonist SQ-30741 reduced ANG II-induced contractions only in SHR of both ages (P < 0.05). Aging increased responses to ANG I in SHR but decreased it in WKY (P < 0.05). In quiescent rings with endothelium, acetylcholine caused contractions in the presence of L-NAME in adult and senescent SHR but not in WKY (P < 0.05). SQ-30741 prevented these contractions (P < 0.05). Contractions to the thromboxane analogue U-46619 were reduced only in senescent SHR (P < 0.05). Thus aging increases and hypertension decreases contractility of smooth muscle in rat mesenteric resistance arteries.(ABSTRACT TRUNCATED AT 250 WORDS)
Lang
M G
MG
Department of Research, University Hospital CH-4054 Basel, Switzerland.
Noll
G
G
Lüscher
T F
TF
D000375:Aging / Q000502:physiology*; D000809:Angiotensins / Q000494:pharmacology; D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives / Q000494:pharmacology; D001158:Arteries / Q000187:drug effects / Q000503:physiopathology*; D001794:Blood Pressure; D001835:Body Weight; D004730:Endothelium, Vascular / Q000503:physiopathology*; D006973:Hypertension / Q000473:pathology / Q000503:physiopathology*; D019331:NG-Nitroarginine Methyl Ester; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009638:Norepinephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014655:Vascular Resistance; D014661:Vasoconstriction; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000809:Angiotensins; D014662:Vasoconstrictor Agents; D011189:Potassium Chloride; D001120:Arginine; D019001:Nitric Oxide Synthase; D019331:NG-Nitroarginine Methyl Ester; D009638:Norepinephrine