Vascular responses after long-term inhibition of nitric oxide synthesis in newborn dogs

The effect of long-term inhibition of nitric oxide synthase on the relaxation and contraction ability of the thoracic aorta, carotid and pulmonary arteries was studied in the early postnatal period. Starting from the fifth day after birth, puppies were administered NG-nitro-L-arginine methyl ester (L-NAME, 50 mg/kg/day subcutaneously) for 6 weeks. After this period, mean blood pressure increased from the control value of 94 +/- 14 mm Hg to 168 +/- 5 mm Hg (P < 0.01) and the heart/body weight ratio from 6.22 +/- 0.25 to 8.23 +/- 0.45 (P < 0.01). In control arterial rings precontracted by phenylephrine (10(-5) mol/l), acetylcholine caused dose-dependent relaxations; the maximal values were reached in the range of 10(-8) to 10(-6) mol/l. In arteries from L-NAME treated puppies, acetylcholine also induced dose-dependent relaxations, the maximum values in the thoracic aorta (81.0 +/- 2.9%) and carotid artery (87.2 +/- 6.9%) were significantly reduced, not, however, in the pulmonary artery (76.4 +/- 7.8%). Dose-response curves to acetylcholine in all the examined arteries from L-NAME-treated animals were shifted to the right indicating a decrease in sensitivity to acetylcholine. Neurogenic contractions, induced by electrical stimulation of adrenergic nerves, were not significantly altered in the thoracic aorta and carotid artery. However, in the pulmonary artery the contractions were greater at high frequency of stimulation. The findings that (i) submaximal doses of L-NAME attenuate acetylcholine-induced relaxation only slightly, and (ii) that it does not appreciably influence adrenergic contractions justify the hypothesis that the endothelium of vessels in newborn dogs is very probably endowed with a high content of nitric oxide synthase.