Departamento de Fisiologia e Farmacologia, Centro de Ciências Biológicas, Universidade Federal de Pernambuco, Av. Prof. Moraes Rêgo, Cidade Universitária, 50670-901, Recife, Brazil.
J Physiol Biochem. 2010 Dec;66(4):301-9. doi: 10.1007/s13105-010-0036-4. Epub 2010 Sep 24.
Spontaneously hypertensive rat (SHR) offspring from L-arginine- and antioxidant-supplemented SHR dams had persistent lower blood pressure in adulthood. We investigated the influence of vascular mechanism in this effect. We analyzed response to acetylcholine and phenylephrine in aorta and superior mesenteric arteries from Wistar-Kyoto (WKY), SHR, and SHR perinatally supplemented with L-arginine and 4-hydroxy-2,2,6,6-tetramethylpiperidinoxyl (TEMPOL; SHR-suppl). Supplements reduced blood pressure persistently in SHR. Relaxation to acetylcholine was greater in WKY than SHR and remained unmodified in SHR-suppl compared with SHR. Acute TEMPOL did not alter relaxation to acetylcholine in WKY but increased it similarly in SHR and SHR-suppl. Phenylephrine contraction was increased in SHR compared to WKY. In SHR-suppl, this response was similar to SHR. Endothelium removal or N-nitro-L-arginine methyl ester (L-NAME) increased contraction to phenylephrine more in WKY than SHR. In SHR-suppl, this was similar to SHR. In both SHR and SHR-suppl, TEMPOL similarly reduced phenylephrine response. This effect was prevented by L-NAME. Results exposed reinforce the concept that oxidative stress during perinatal period is a contributing factor to the development of hypertension in SHR. Results also reveal that the beneficial effect of this supplementation does not appear to be related to improved endothelial function, suggesting that other regulatory mechanisms of blood pressure may be involved.
自发性高血压大鼠(SHR)后代的母鼠在孕期补充 L-精氨酸和抗氧化剂后,成年后血压持续较低。我们研究了血管机制在这种效应中的影响。我们分析了 Wistar-Kyoto(WKY)大鼠、SHR 大鼠和孕期补充 L-精氨酸和 4-羟基-2,2,6,6-四甲基哌啶氧自由基(TEMPOL;SHR-suppl)的 SHR 大鼠主动脉和肠系膜上动脉对乙酰胆碱和苯肾上腺素的反应。补充剂持续降低 SHR 的血压。WKY 大鼠对乙酰胆碱的松弛反应大于 SHR,而与 SHR 相比,SHR-suppl 则保持不变。急性 TEMPOL 不改变 WKY 大鼠对乙酰胆碱的松弛反应,但对 SHR 和 SHR-suppl 有相似的增加作用。与 WKY 大鼠相比,SHR 大鼠的苯肾上腺素收缩增加。在 SHR-suppl 中,这种反应与 SHR 相似。内皮去除或 N-硝基-L-精氨酸甲酯(L-NAME)使 WKY 大鼠对苯肾上腺素的收缩反应增加多于 SHR 大鼠。在 SHR-suppl 中,这种情况与 SHR 相似。在 SHR 和 SHR-suppl 中,TEMPOL 相似地降低了苯肾上腺素的反应。这种作用被 L-NAME 阻止。结果进一步证实了这样一个概念,即在围产期氧化应激是 SHR 高血压发展的一个促成因素。结果还表明,这种补充的有益效果似乎与改善内皮功能无关,提示可能涉及其他调节血压的机制。