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 rel axation and contraction ability of the thoracic aorta, carotid and pul monary arteries was studied in the early postnatal period. Starting fr om the fifth day after birth, puppies were administered N-G-nitro-L-ar ginine methyl ester (L-NAME, 50 mg/kg/day subcutaneously) for 6 weeks. After this period, mean blood pressure increased from the control val ue of 94+/-14 mm Hg to 168+/-5 mm Hg (P<0.01) and the heart/body weigh t 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 cau sed 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 pupp ies, acetylcholine also induced dose-dependent relaxations, the maximu m values in the thoracic aorta (81.0+/-2.9 %) and carotid artery (87.2 +/-6.9 %) were significantly reduced, not, however, in the pulmonary a rtery (76.4+/-7.8 %). Dose-response curves to acetylcholine in all the examined arteries from L-NAME-treated animals were shifted to the rig ht indicating a decrease in sensitivity to acetylcholine. Neurogenic c ontractions, induced by electrical stimulation of adrenergic nerves, w ere not significantly altered in the thoracic aorta and carotid artery . However, in the pulmonary artery the contractions were greater at hi gh 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 ju stify the hypothesis that the endothelium of vessels in newborn dogs i s very probably endowed with a high content of nitric oxide synthase.