Briones Ana M, Alonso María J, Hernanz Raquel, Miguel Marta, Salaices Mercedes
Departamento de Farmacología y Terapéutica, Facultad de Medicina, Universidad Autónoma de Madrid, C/ Arzobispo Morcillo 4, Madrid, Spain.
J Cardiovasc Pharmacol. 2002 Mar;39(3):378-88. doi: 10.1097/00005344-200203000-00009.
Hypertension-associated alterations of the nitric oxide (NO) pathway were analyzed in middle cerebral arteries (MCA) from normotensive (WKY) and hypertensive (SHR) rats. The vasoconstrictor response to prostaglandin F2alpha (PGF(2 alpha), 30 and 100 microM) was smaller in MCA from SHR than from WKY. Endothelium-dependent relaxations to bradykinin (1 nM-10 microM) or acetylcholine (10 microM) were similar in MCA from both strains, whereas the endothelium-independent response to sodium nitroprusside (1 nM-0.1 mM) was smaller in MCA from SHR. L-arginine (L-Arg, 10 microM) similarly inhibited the vasoconstrictor responses in both strains; however, the inhibitory effect of 100 microM of L-Arg was greater in MCA from SHR. N(omega)-nitro-L-arginine methyl ester (L-NAME, 100 microM), but not aminoguanidine (100 microM) or 7-nitroindazole (10 microM), increased basal tone, potentiated the PGF(2 alpha)-induced vasoconstrictor responses and reduced the bradykinin-elicited relaxation in a similar way in MCA from WKY and SHR. N(omega)-nitro-L-arginine methyl ester also antagonized the inhibitory effect of 10 microM of L-Arg. Incubation for 5 h with lipopolysaccharide (10 microg/ml) similarly reduced the response to PGF(2 alpha) in MCA from WKY and SHR; this reduction was antagonized by dexamethasone (1 microM). Cerebral arteries expressed endothelial (eNOS) and neuronal (nNOS) NO synthase similarly in both strains, but inducible NOS (iNOS) expression was more evident in SHR. Lipopolysaccharide increased iNOS expression in both strains to a similar level. The basal constitutive NOS (cNOS) and iNOS activities were similar in arteries from WKY and SHR. Lipopolysaccharide increased iNOS activity only in arteries from SHR. These results indicate that hypertension did not impair endothelial NO production by NOS activation but induced an up-regulation of basal iNOS expression.
在正常血压（WKY）大鼠和高血压（SHR）大鼠的大脑中动脉（MCA）中分析了与高血压相关的一氧化氮（NO）途径改变。与WKY大鼠相比，SHR大鼠MCA对前列腺素F2α（PGF(2α)，30和100μM）的血管收缩反应较小。两种品系大鼠MCA对缓激肽（1 nM - 10μM）或乙酰胆碱（10μM）的内皮依赖性舒张相似，而SHR大鼠MCA对硝普钠（1 nM - 0.1 mM）的非内皮依赖性反应较小。L - 精氨酸（L - Arg，10μM）在两种品系中均类似地抑制血管收缩反应；然而，100μM的L - Arg对SHR大鼠MCA的抑制作用更强。N(ω)-硝基 - L - 精氨酸甲酯（L - NAME，100μM），而非氨基胍（100μM）或7 - 硝基吲唑（10μM），以类似方式增加WKY和SHR大鼠MCA的基础张力，增强PGF(2α)诱导的血管收缩反应并减少缓激肽引起的舒张。N(ω)-硝基 - L - 精氨酸甲酯也拮抗10μM的L - Arg的抑制作用。用脂多糖（10μg/ml）孵育5小时同样降低了WKY和SHR大鼠MCA对PGF(2α)的反应；这种降低被地塞米松（1μM）拮抗。两种品系的脑动脉中内皮型（eNOS）和神经元型（nNOS）一氧化氮合酶的表达相似，但诱导型一氧化氮合酶（iNOS）在SHR大鼠中表达更明显。脂多糖使两种品系中的iNOS表达增加到相似水平。WKY和SHR大鼠动脉中的基础组成型一氧化氮合酶（cNOS）和iNOS活性相似。脂多糖仅增加SHR大鼠动脉中的iNOS活性。这些结果表明，高血压并未通过一氧化氮合酶激活损害内皮一氧化氮生成，但诱导基础iNOS表达上调。
