Acute intravenous injection and short-term oral administration of N(G) -nitro-L-arginine methyl ester to the rat provoke increased pressor responses to agonists and hypertension, but not inhibition of acetylcholine-induced hypotensive responses.
In experiments in vivo, we studied whether the endothelial dysfunction induced by nitric oxide (NO) synthesis inhibition is simultaneously or sequentially manifested as a reduced level of endothelium-dependent agonist-induced vasodilatation, an increased responsiveness to vasoconstrictors, and hypertension. Vascular responses to acetylcholine, phenylephrine, and angiotensin II were measured in pithed rats after acute intravenous injection (100 mg/kg) and short-term oral administration of N(G) -nitro-L-arginine methyl ester (L-NAME; 60 mg/kg per day) for 1 and 3 days (L-NAME(1d) and L-NAME(3d), respectively). Pithed rats were chosen because drug-induced cardiovascular responses reflect only peripheral effects. Parallel experiments examined mean arterial pressure (MAP) values in anesthetized rats. After short-term L-NAME(1d) and L-NAME(3d) treatments, the MAP was significantly elevated in anesthetized but not pithed rats. Acute intravenous administration of L-NAME elevated MAP in pithed rats. Intravenous infusion of phenylephrine was used to compensate for the pressor response induced by L-NAME in pithed animals. The maximum decrease and duration of the hypotensive responses to acetylcholine were unaltered by the acute and both short-term L-NAME treatments in pithed rats. These treatments, on the other hand, increased phenylephrine- and angiotensin II-induced pressor responses in pithed animals. In isolated aortic rings prepared from pithed rats treated acutely and short-term with L-NAME, acetylcholine-induced relaxations were inhibited. Thus, the inhibition of NO-dependent vasodilator tone after acute intravenous injection and short-term oral L-NAME administration may be associated with vascular smooth muscle hyper-responsiveness to pressor agonists and hypertension, whereas the hypotensive responses to acetylcholine could not be associated with the L-NAME-induced endothelial dysfunction in pithed rats.
López
Ruth M
RM
Sección de Estudios de Posgrado e Investigación, Escuela Superior de Medicina, Instituto Politécnico Nacional, México, D.F., México.
Pérez
Teresa
T
Castillo
Carlos
C
Castillo
María C
MC
Castillo
Enrique F
EF
D000109:Acetylcholine / Q000037:antagonists & inhibitors / Q000494:pharmacology*; D000284:Administration, Oral; D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects*; D004730:Endothelium, Vascular / Q000187:drug effects; D004791:Enzyme Inhibitors / Q000008:administration & dosage; D006973:Hypertension / Q000139:chemically induced* / Q000188:drug therapy*; D007022:Hypotension / Q000139:chemically induced* / Q000188:drug therapy; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage*; D009569:Nitric Oxide / Q000037:antagonists & inhibitors / Q000378:metabolism; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism; D010656:Phenylephrine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014661:Vasoconstriction / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D004791:Enzyme Inhibitors; D000804:Angiotensin II; D010656:Phenylephrine; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D000109:Acetylcholine; D019331:NG-Nitroarginine Methyl Ester