Heterogeneity of endothelium-dependent vasorelaxation in conductance and resistance arteries from Lyon normotensive and hypertensive rats.
OBJECTIVE
The nature of endothelial factors in response to acetylcholine (ACh) was investigated in conductance and resistance arteries from Lyon normotensive (LN) and Lyon hypertensive (LH) rats. Differences in endothelial function between the two strains were evaluated.


METHODS
Relaxations to ACh were studied in the aorta and small mesenteric arteries (SMA). The relative contribution of nitric oxide (NO), prostanoids and endothelial-derived hyperpolarizing factor (EDHF) was assessed using appropriate inhibitors. Western blot of endothelial NO synthase was achieved. The membrane potential of smooth muscle cells was assessed using microelectrodes.


RESULTS
In LN rats, endothelium-dependent relaxation to ACh involved exclusively NO in the aorta, whereas both NO and EDHF were implicated in SMA. In the latter, relaxation was almost entirely prevented by blockade of either the NO or EDHF pathway, although ACh was still able to produce hyperpolarization in the presence of NO synthase and cyclooxygenase inhibitors. In LH rats, relaxation to ACh was unchanged in SMA but moderately depressed in the aorta, despite unchanged endothelial NO synthase protein expression and sensitivity to NO. In addition, indomethacin, but not a selective cyclooxygenase-2 inhibitor, significantly reduced ACh relaxations in the aorta from LH rats but not from LN rats.


CONCLUSIONS
These results document differential endothelial function in a conductance and in resistance arteries from LN rats and LH rats. They show that simultaneous participation of NO and EDHF is required to promote relaxation in SMA from both strains, whereas NO alone accounts for relaxation in aorta from LN rats. In LH rats, aortic relaxation induced by ACh is slightly decreased despite the involvement of vasodilator products from cyclooxygenase-1.
Freitas
Maria Regina
MR
Laboratoire de Pharmacologie et Physico-Chimie des Interactions Cellulaires et Moléculaires, Université Louis Pasteur de Strasbourg, Faculté de Pharmacie, Illkirch, France.
Schott
Christa
C
Corriu
Catherine
C
Sassard
Jean
J
Stoclet
Jean-Claude
JC
Andriantsitohaina
Ramaroson
R
D000109:Acetylcholine / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000502:physiology; D001685:Biological Factors / Q000378:metabolism; D001794:Blood Pressure; D001835:Body Weight; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006973:Hypertension / Q000378:metabolism / Q000503:physiopathology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D018384:Oxidative Stress / Q000187:drug effects / Q000502:physiology; D011453:Prostaglandins / Q000378:metabolism; D051381:Rats; D011919:Rats, Inbred Strains; D011922:Rats, Mutant Strains; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology*; D014665:Vasodilator Agents / Q000494:pharmacology
D001685:Biological Factors; D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D011453:Prostaglandins; D014665:Vasodilator Agents; C067410:endothelium-dependent hyperpolarization factor; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine