Abstract:
: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.
journal_name
Fundam Clin Pharmacoljournal_title
Fundamental & clinical pharmacologyauthors
López RM,Pérez T,Castillo C,Castillo MC,Castillo EFdoi
10.1111/j.1472-8206.2010.00852.xsubject
Has Abstractpub_date
2011-06-01 00:00:00pages
333-42issue
3eissn
0767-3981issn
1472-8206pii
FCP852journal_volume
25pub_type
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