The sympathetic nervous system: the muse of primary hypertension.
Von Euler characterised the sympathetic neurotransmitter noradrenaline (NA) and postulated that excessive neural tone was a cause of primary hypertension (PH). Thirty years ago, we found raised NA levels in 30-40% of young patients with PH. Laragh found plasma renin activity (PRA) a risk marker for coronary artery disease. With Esler, Miura, and Campese, a close association was found of plasma NA with PRA. We found raised tyrosine hydroxylase activity (AC) in the hearts of a rabbit model of sinoaortic denervated hypertension and in PH with raised plasma NA. Esler utilised titrated NA infusion and described increased spillover of NA from heart, kidney and subcortical areas of brain of patients with PH. With Eide we found raised cerebrospinal fluid (CSF) NA in PH (not secondary hypertension) and with Kolloch and Miura, we found raised plasma/CSF NA in conjunction with reduced dopaminergic tone. With Shkvatsabaya, Yurenev and Davison, we found that relaxation therapy improved the anger ambience and blood pressure of PH with raised plasma NA vs those with normal NA levels. Campese found a hypothalamic source of raised blood pressure in two rat models - microphenol treated and ischaemic kidney. The resulting hypertension was associated with raised NA turnover of their hypothalamic centres. Finally, with Hsueh and Hodis, we found raised plasma NA in association with insulin resistance increased left ventricular mass and intimal medial hypertrophy in Mexican-American diabetics and their yet unaffected offspring. Reliable estimates of human sympathetic AC, including levels of plasma NA in the effluent of selected organs and peripheral venous and arterial sites, may eventually be displaced by techniques using genetic analysis and molecular biology. Never the less, the sympathetic nervous system appears to play an important role in the pathogenesis, sequelae and therapy of PH.
DeQuattro
V
V
Keck School of Medicine, University of Southern California, Los Angeles, California, USA.
Feng
M
M
D000818:Animals; D006801:Humans; D006973:Hypertension / Q000503:physiopathology*; D009638:Norepinephrine / Q000097:blood; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D009638:Norepinephrine