Nitric oxide mediates inhibitory effect of losartan on angiotensin-induced contractions in hamster but not rat aorta.
We investigated a possible contribution of nitric oxide (NO) and prostaglandins to the inhibitory effect of losartan on contractions to Ang I (10(-6) M) and Ang II (10(-7) M) with or without L-NAME (10(-4) M) or indomethacin (10(-5) M) in the aorta of WKY, SHR and hamster (n=7 each). Rings of thoracic aorta (2-mm long) were placed in a myograph (5 ml). Endothelium-dependent vasodilations were evaluated with acetylcholine (10(-8) to 10(-6) M). After a 45-minute incubation with L-NAME under a resting tension of 2 g, only hamster aorta contracted (p<0.01). The SHR aorta showed impaired relaxations to acetylcholine compared with the WKY and hamster aorta (p<0.05). Despite the difference in the stimulated NO release, losartan completely abolished the responses to Ang I and Ang II both in WKY and SHR vessels irrespective of the presence of L-NAME. In contrast to the rat aorta, the inhibitory effect of losartan was attenuated in the presence of L-NAME in the hamster aorta (78% vs 99% inhibition, p<0.05). Indomethacin did not alter the effect of losartan in any vessels. Our results suggest that the presence of NO, particularly a basal secretion of NO, is necessary for the full expression of the inhibitory effect of losartan in the hamster, but not in WKY or SHR, aorta. Unlike NO, prostaglandins do not appear to play a role in the effect of losartan.
Inoue
K
K
Third Department of Internal Medicine, Osaka Medical College, Osaka, 569-8686, Japan.
Nishimura
H
H
Kubota
J
J
Kitaura
Y
Y
D000809:Angiotensins / Q000494:pharmacology*; D000818:Animals; D001011:Aorta / Q000187:drug effects* / Q000502:physiology; D006224:Cricetinae / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D008647:Mesocricetus; D019331:NG-Nitroarginine Methyl Ester / Q000494:pharmacology; D009569:Nitric Oxide / Q000502:physiology*; D051381:Rats / Q000502:physiology*; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013045:Species Specificity; D014661:Vasoconstriction / Q000187:drug effects*
D000809:Angiotensins; D004791:Enzyme Inhibitors; D009569:Nitric Oxide; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester