Endothelial nitric oxide weakens arterial contractile responses and reduces blood pressure during early postnatal development in rats.
OBJECTIVE
During maturation the vascular system undergoes structural and functional remodeling. At the systemic level it results in a gradual increase of arterial blood pressure during postnatal ontogenesis. The mechanisms of maintaining the blood pressure at a comparatively low level during the early postnatal development are not completely understood. Recently we showed that the hindlimb arteries of young (1-2 wk-old) rats exhibited an enhanced endothelial NO-pathway activity, which weakened their contractile responsiveness compared to the arteries of adult rats. Here we tested the hypothesis that an increased tonic endothelial NO production can take place in the whole vascular system leading to a decreased level of systemic blood pressure in young rats.


DESIGN AND METHODS
Segments of small mesenteric, saphenous, sural and intrarenal arteries were isolated from the young (2 wk-old), juvenile (4 wk-old) and adult (10-12 wk-old) male rats and tested in a wire isometric myograph. Anticontractile effect of NO was evaluated by the effects of NOS inhibitor L-NNA on both arterial spontaneous tone and constrictor responses to methoxamine (α1-adrenoceptor agonist). In addition, eNOS and arginase-2 mRNA expression in arterial preparations by qPCR and serum nitrite/nitrate levels by Griess reaction were estimated. Blood pressure with an intra-carotid artery catheter was measured in conscious rats.


RESULTS
In all arteries of 2 wk rats except the renal ones, L-NNA exposure resulted in a considerable tonic contraction and a remarkable enhancement of contractile responses to methoxamine. The effect of L-NNA gradually decreased with age and by 10-12 weeks became very small in the mesenteric arteries and disappeared in the sural and saphenous arteries. Although no difference in eNOS mRNA expression was found, the content of arginase-2 mRNA was significantly lower in young rats compared to adults. Serum levels of NO metabolites were two-fold higher in 2 wk-old rats than in adult rats. Along with that, arterial blood pressure was by half lower but rose more prominently after administration of l-NAME in young rats than in adults.


CONCLUSIONS
In young rats, tonic release of NO by the endothelium considerably weakens contractile responses of arteries supplying intestine, skin and skeletal muscles, which receive a high proportion of the cardiac output. Such anticontractile effect of NO can be an important mechanism responsible for the blood pressure reduction in immature circulatory system.
['Sofronova|Svetlana I|SI|', 'Borzykh|Anna A|AA|', 'Gaynullina|Dina K|DK|', 'Kuzmin|Ilya V|IV|', 'Shvetsova|Anastasia A|AA|', 'Lukoshkova|Elena V|EV|', 'Tarasova|Olga S|OS|']
D000367:Age Factors D000818:Animals D001119:Arginase D062186:Arterial Pressure D001158:Arteries D004730:Endothelium, Vascular D006834:Hydrazines D008297:Male D009119:Muscle Contraction D009131:Muscle, Smooth, Vascular D019331:NG-Nitroarginine Methyl Ester D009566:Nitrates D009569:Nitric Oxide D020030:Nitric Oxide Donors D019001:Nitric Oxide Synthase D052250:Nitric Oxide Synthase Type III D009573:Nitrites D019335:Nitroarginine D012333:RNA, Messenger D017208:Rats, Wistar
Nitric oxide Postnatal development eNOS Endothelium Arterial pressure Resistance arteries