title: Effects of NG-nitro-L-arginine methyl ester on vasodilator responses to adrenaline or BRL 38227 in conscious rats.
abstract: 1. Conscious, Long Evans rats, chronically instrumented for the measurement of regional haemodynamics, were used to assess responses to 3 min infusions of the potassium channel opener, BRL 38227 (1 and 10 micrograms kg-1 min-1) or adrenaline (0.05 and 0.5 microgram kg-1 min-1) in the absence and in the presence of NG-nitro-L-arginine methyl ester (L-NAME; 3 mg kg-1 h-1), an inhibitor of nitric oxide biosynthesis. 2. In the absence of L-NAME, the low dose of BRL 38227 caused slight hypotension and tachycardia, accompanied by small increases in mesenteric and hindquarters blood flow only. However, there were increases in renal, mesenteric and hindquarters vascular conductances. L-NAME had no effect on any of these responses. 3. The high dose of BRL 38227 caused substantial hypotension and tachycardia. Renal and hindquarters flows did not change significantly, but there was a marked increase in mesenteric flow. There were only modest increases in renal and hindquarters vascular conductances but a substantial mesenteric vasodilatation. In the presence of L-NAME, there was a slight reduction of the latter but no other changes in the responses to BRL 38227. 4. In the absence of L-NAME, the low dose of adrenaline caused slight hypotension but a marked tachycardia. There were no changes in renal or mesenteric blood flow but a clear-cut increase in hindquarters flow. Renal and mesenteric vascular conductances showed only small rises, in contrast to the substantial hindquarters vasodilatation. In the presence of L-NAME, there was significant attenuation of the tachycardia and of the increases in hindquarters flow and vascular conductance in response to adrenaline.5. The high dose of adrenaline caused marked hypotension and tachycardia. Renal flow did not change, but there was a fall in mesenteric and a marked rise in hindquarters flow. Renal vascular conductance showed a slight increase but mesenteric vascular conductance did not change significantly, whereas there was a substantial hindquarters vasodilatation. In the presence of L-NAME, adrenaline caused an increase in blood pressure but no significant change in heart rate; the renal vasodilatation was abolished, there was a mesenteric vasoconstriction, and the hindquarters vasodilatation was markedly reduced. L-NAME also attenuated the tachycardia induced by adrenaline in animals with no cardiac baroreflexes.6. The present results indicate that L-NAME-sensitive mechanisms are involved in the vasodilator and tachycardic effects of adrenaline. The relative lack of effect of L-NAME on responses to BRL 38227 indicates that the changes in the responses to adrenaline were not non-specific or due to changes in haemodynamic status caused by L-NAME. The results raise the possibility that the 'hypertensinogenic' properties of endogenous adrenaline could be amplified when nitric oxide biosynthesis is impaired.
authors.affiliation: Department of Physiology and Pharmacology, University of Nottingham Medical School, Queen's Medical Centre.
authors.forename: S M
authors.initials: SM
authors.lastname: Gardiner
authors.forename: P A
authors.initials: PA
authors.lastname: Kemp
authors.forename: T
authors.initials: T
authors.lastname: Bennett
mesh_terms: D000818:Animals; D001120:Arginine / Q000031:analogs & derivatives* / Q000494:pharmacology; D001578:Benzopyrans / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D019806:Cromakalim; D004837:Epinephrine / Q000494:pharmacology*; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D011758:Pyrroles / Q000494:pharmacology*; D051381:Rats; D012039:Regional Blood Flow / Q000187:drug effects; D014665:Vasodilator Agents / Q000494:pharmacology*
chemical_list: D001578:Benzopyrans; D011758:Pyrroles; D014665:Vasodilator Agents; D019806:Cromakalim; D001120:Arginine; D019331:NG-Nitroarginine Methyl Ester; D004837:Epinephrine