Nasal vasoconstriction and decongestant effects of nitric oxide synthase inhibition in the pig.
The effects of systemic administration of the nitric oxide synthase inhibitor N omega-nitro-L-arginine on the vasculature of the pig nasal mucosa were compared with the effects of alpha-adrenoceptor agonists and of sympathetic nerve stimulation. A novel in vivo pig model was used in which standard measurements of nasal mucosal blood flow were complemented with measurements of nasal cavity volume using an acoustic rhinometer. The vasodilatory effects of capsaicin, substance P. acetylcholine, vasoactive intestinal polypeptide and nitroprusside, before and after nitric oxide synthase inhibition, were also investigated. N omega-nitro-L-arginine evoked a marked, slowly developing, long-lasting reduction in nasal vascular conductance with a parallel increase in nasal cavity volume (by approximately 30%) comparable in magnitude with the response upon alpha-adrenoceptor stimulation. L-Arginine partly reversed the N omega-nitro-L-arginine-evoked vasoconstriction, although nasal cavity volume was unaffected. Nasal vasodilation and decrease in nasal cavity volume resulting from capsaicin-evoked activation of sensory nerves were unaltered after administration of N omega-nitro-L-arginine. Nitric oxide synthase inhibition did not attenuate the vasodilator responses evoked by either substance P. acetylcholine, vasoactive intestinal polypeptide or nitroprusside. The present data suggest that nitric oxide synthase activity is of importance both for basal nasal vascular conductance and nasal cavity volume in the pig in vivo. In contrast, nitric oxide synthase inhibition does not reduce the vascular effects of a variety of vasodilating agents, including capsaicin, acetylcholine and substance P.
Rinder
J
J
Department of Physiology and Pharmacology, Karolinska Institute, Stockholm, Sweden.
Lundberg
J M
JM
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000403:Airway Resistance / Q000187:drug effects / Q000502:physiology; D000818:Animals; D004558:Electric Stimulation; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005260:Female; D008297:Male; D009129:Muscle Tonus / Q000187:drug effects / Q000502:physiology; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000201:enzymology; D009296:Nasal Cavity / Q000033:anatomy & histology / Q000187:drug effects; D014663:Nasal Decongestants / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors*; D019335:Nitroarginine / Q000494:pharmacology*; D013552:Swine; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000502:physiology
D000316:Adrenergic alpha-Agonists; D004791:Enzyme Inhibitors; D014663:Nasal Decongestants; D018377:Neurotransmitter Agents; D019335:Nitroarginine; D019001:Nitric Oxide Synthase