Cabassi Aderville, Dancelli Simona, Pattoneri Paolo, Tirabassi Giovanni, Quartieri Fabio, Moschini Luigi, Cavazzini Stefania, Maestri Roberta, Lagrasta Costanza, Graiani Gallia, Corradi Domenico, Parenti Elisabetta, Tedeschi Stefano, Cremaschi Elena, Coghi Pietro, Vinci Simonetta, Fiaccadori Enrico, Borghetti Alberico
Laboratory of Hypertension, Department of Internal Medicine, Nephrology and Health Sciences, University of Parma, Parma, Italy.
J Hypertens. 2007 Aug;25(8):1719-30. doi: 10.1097/HJH.0b013e3281de72f0.
Left ventricular hypertrophy in human and experimental hypertension is not always associated with pressure overload but seems to precede an increase in blood pressure. In this study, performed in male 5-week-old prehypertensive spontaneously hypertensive rats (SHR; n = 65) and age-matched Wistar-Kyoto rats (n = 56), the relationship between myocardial structure and activation of the adrenergic and nitric oxide systems was evaluated.
Body weight, blood pressure and heart rate were similar in both groups. A higher left ventricle/body weight ratio was found in SHR, as a result of greater mononuclear (+47%) and binuclear (+43%) myocyte volumes, without changes in interstitial collagen. Both adrenergic and nitric oxide pathways were activated in SHR, as expressed by higher myocardial norepinephrine content, tyrosine hydroxylase activity, myocardial nitric oxide synthase 3 expression and protein nitration, indicating greater peroxynitrite (ONOO) generation from nitric oxide and superoxide. No difference was measured in nitric oxide synthase 1 expression, whereas nitric oxide synthase 2 was undetectable. A positive correlation between myocardial tyrosine hydroxylase activity and protein nitration was observed in SHR (r = 0.328; P < 0.01). Early treatment with a superoxide dismutase mimetic, 4-hydroxy-2,2,6,6-tetramethyl piperidinoxyl, from the third to the fifth week of age, reduced ONOO generation, protein nitration and sympathetic activation in SHR without changes in myocardial structure.
In prehypertensive SHR, left ventricular hypertrophy is associated with adrenergic and nitrosative imbalance. Early superoxide dismutase mimetic treatment in SHR effectively reduces higher myocardial ONOO generation, sympathetic activation, and heart rate without affecting the development of myocardial hypertrophy.
人类和实验性高血压中的左心室肥厚并不总是与压力超负荷相关，而是似乎先于血压升高出现。在本研究中，对5周龄的雄性高血压前期自发性高血压大鼠（SHR；n = 65）和年龄匹配的Wistar - Kyoto大鼠（n = 56）进行实验，评估心肌结构与肾上腺素能系统和一氧化氮系统激活之间的关系。
两组大鼠的体重、血压和心率相似。SHR的左心室/体重比更高，这是由于单核（+47%）和双核（+43%）心肌细胞体积增大，而间质胶原无变化。SHR中的肾上腺素能和一氧化氮途径均被激活，表现为心肌去甲肾上腺素含量、酪氨酸羟化酶活性、心肌一氧化氮合酶3表达和蛋白质硝化作用升高，表明一氧化氮和超氧化物生成的过氧亚硝酸盐（ONOO）增加。一氧化氮合酶1表达无差异，而一氧化氮合酶2未检测到。在SHR中观察到心肌酪氨酸羟化酶活性与蛋白质硝化作用之间呈正相关（r = 0.328；P < 0.01）。从第3周到第5周龄用超氧化物歧化酶模拟物4 - 羟基 - 2,2,6,6 - 四甲基哌啶氮氧化物进行早期治疗，可减少SHR中的ONOO生成、蛋白质硝化作用和交感神经激活，而心肌结构无变化。
在高血压前期SHR中，左心室肥厚与肾上腺素能和亚硝化失衡有关。对SHR进行早期超氧化物歧化酶模拟物治疗可有效降低心肌中较高的ONOO生成、交感神经激活和心率，而不影响心肌肥厚的发展。
