Role for nitric oxide but not prostaglandins in acetylcholine-induced relaxation of rat cremaster third-order arterioles in 5-hour ischemia-reperfusion control rats.
Intravital videomicroscopy was used for 1 hr in anesthetized 4- to 5-week-old rats, while mean femoral arterial blood pressure and suffusate Po2 were continuously monitored. The total duration for experimentation was 5 hr in order to mimic the controls used previously for a 4-hr ischemia and 1-hr reperfusion model. The specific aim was to examine further the efficacy of this model by (a) assessing the potential role(s) of nitric oxide (NO) and/or prostaglandins (PG) in acetylcholine (ACh)-induced relaxation, and (b) determining if inherently low vasomotor tone (VT) and wall shear stress (WSS) mask latent NO- and/or PG-mediated responses to ACh. Reactivity to 10(-4) M ACh or 10(-6) M sodium nitroprusside (NP) were determined in resting third-order arterioles (3A) or in those preconstricted with norepinephrine (10(-6) M NE) at physiological suffusate Po2 (25-30 mm Hg). Repeated and randomized topical administrations of ACh, NP, arachidonic acid (10(-5) M AA), NE, or 10(-5) M atropine (ATR), NG-nitro-L-arginine methyl ester (L-NAME), or ibuprofen (Ib) alone or in combination to the surface of exteriorized cremaster flaps, provoked no alteration in mean systemic arterial blood pressure. ACh and NP were equipotent evoking relaxations on the same order of magnitude and duration as reported previously for arterioles with spontaneous or NE-enhanced VT. ATR or L-NAME decreased resting internal diameter by 12 to 14% and reversed relaxation of resting or preconstricted arterioles to ACh but not to NP. Ib failed to elicit blockade. However, administration of AA demonstrated Ib-inhibitable increases of 20 and 52% in resting and NE-preconstricted arterioles, respectively, implicating NO but not PG in the regulation of resting (relaxant) tone and in ACh-induced dilation following activation of 3A muscarinic receptors. The absence of PG-mediated responses appears unrelated to low initial WSS at physiologic suffusate Po2, since NE-induced elevations of VT and centerline cell velocity also did not cause Ib-inhibitable relaxation. These and our previous findings suggest that the impaired relaxant function of 3A arterioles is caused in part by a paucity in spontaneous tone inherent to this model and by depressed vasoreactivity arising from disruption of NO biosynthesis.
Department of Anatomy, School of Medicine, Robert C. Byrd Health Sciences Center, West Virginia University, Morgantown 26506, USA.
D M
DM
Borsch
E V
EV
Cilento
F D
FD
Reilly
D000109:Acetylcholine / Q000494:pharmacology*; D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D001160:Arterioles; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009126:Muscle Relaxation / Q000502:physiology; D009129:Muscle Tonus; D018482:Muscle, Skeletal / Q000098:blood supply*; D009131:Muscle, Smooth, Vascular / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology*; D020030:Nitric Oxide Donors / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000494:pharmacology; D011453:Prostaglandins / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology*; D013314:Stress, Mechanical; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D016861:Cyclooxygenase Inhibitors; D004791:Enzyme Inhibitors; D018727:Muscarinic Antagonists; D020030:Nitric Oxide Donors; D011453:Prostaglandins; D014662:Vasoconstrictor Agents; D009599:Nitroprusside; D016718:Arachidonic Acid; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D009638:Norepinephrine