Fregly M J, Rossi F, Sun Z, Tümer N, Cade J R, Hegland D, Yürekli M
Department of Physiology, University of Florida, College of Medicine, Gainesville 32610-0274.
Pharmacology. 1994 Dec;49(6):351-62. doi: 10.1159/000139254.
Chronic exposure to cold (5 degrees C) is well known to increase both tyrosine hydroxylase (TH) activity in brown adipose tissue and systemic blood pressure. The effect of chronic dietary administration of the alpha-adrenergic antagonist, prazosin, and the amino acid, L-arginine, on both the elevation of blood pressure during exposure to cold and on TH activity and expression of TH mRNA in the adrenal glands of rats was studied. As observed previously, chronic exposure to cold increased systolic blood pressure significantly and induced cardiac hypertrophy. Chronic dietary treatment with prazosin (8 mg/kg food) and arginine (20 g/kg food) returned blood pressure to control levels, did not affect body weight significantly, but failed to prevent cardiac hypertrophy. Both prazosin and L-arginine reduced the drinking response to administration of angiotensin II. Treatment with arginine and prazosin was accompanied by a significant increase in the urinary outputs of dopamine and L-DOPA. The 3 cold-treated groups (control, L-arginine and prazosin) had increases in plasma T3 and decreases in plasma T4 and plasma renin activity. Plasma concentrations of epinephrine and norepinephrine were increased significantly in the L-arginine-treated group. TH mRNA and TH activity in the adrenal glands were increased in the 3 cold-treated groups and these measures were correlated directly and significantly with plasma norepinephrine and epinephrine concentrations. Although both prazosin and arginine prevented the cold-induced elevation of blood pressure, they did not prevent the increase in TH mRNA, TH activity or epinephrine in plasma. The protective effect of arginine and prazosin in cold-induced hypertension may be related both to their reduction in plasma renin activity and to a reduced responsiveness to angiotensin II, as well as to their abilities to increase the secretion of dopamine.
众所周知,长期暴露于寒冷环境(5摄氏度)会增加棕色脂肪组织中的酪氨酸羟化酶(TH)活性以及全身血压。本研究探讨了长期饮食给予α-肾上腺素能拮抗剂哌唑嗪和氨基酸L-精氨酸,对大鼠暴露于寒冷环境期间血压升高以及肾上腺中TH活性和TH mRNA表达的影响。如先前观察到的,长期暴露于寒冷环境会显著升高收缩压并诱发心脏肥大。用哌唑嗪(8毫克/千克食物)和精氨酸(20克/千克食物)进行长期饮食治疗可使血压恢复至对照水平,对体重无显著影响,但未能预防心脏肥大。哌唑嗪和L-精氨酸均降低了对血管紧张素II给药的饮水反应。精氨酸和哌唑嗪治疗伴随多巴胺和L-多巴尿排出量显著增加。3个寒冷处理组(对照组、L-精氨酸组和哌唑嗪组)的血浆T3升高,血浆T4和血浆肾素活性降低。L-精氨酸治疗组的血浆肾上腺素和去甲肾上腺素浓度显著升高。3个寒冷处理组肾上腺中的TH mRNA和TH活性均增加,且这些指标与血浆去甲肾上腺素和肾上腺素浓度直接且显著相关。尽管哌唑嗪和精氨酸均能预防寒冷诱导的血压升高,但它们并未阻止血浆中TH mRNA、TH活性或肾上腺素的增加。精氨酸和哌唑嗪对寒冷诱导的高血压的保护作用可能与其降低血浆肾素活性、降低对血管紧张素II的反应性以及增加多巴胺分泌的能力有关。