title: Autonomic nervous system and adrenergic receptors in chronic hypotensive haemodialysis patients.
abstract: BACKGROUND
  The pathophysiology of chronic hypotension (CH) in uraemia is not elucidated. The possible role of autonomic nervous system dysfunction and adrenoceptor alterations in the pathophysiology of CH in uraemia was evaluated in this study.
  
  
  METHODS
  Seventeen hypotensive haemodialysis (HD) patients, 17 normotensive HD patients, and 17 control subjects were studied. We evaluated the integrity of the baroreflex arc (Valsalva manoeuvre), the parasympathetic efferent pathway ('deep-breathing test') and the sympathetic efferent pathway ('hand-grip test'). We also evaluated platelet alpha 2-adrenoceptor and lymphocyte beta 2-adrenoceptor densities (radioligand binding assay), and beta 2-adrenoceptor response (intracellular cAMP generation after isoproterenol stimulation in lymphocytes).
  
  
  RESULTS
  Responses to the Valsalva manoeuvre and the deep-breathing test were altered in all HD patients (P < 0.05). Valvalva ratio was lower in hypotensive patients than in normotensive patients (P < 0.01), whereas the pressor response to the hand-grip test was reduced only in hypotensive HD patients (P < 0.01). In haemodialysed patients, basal mean blood pressure (MBP) correlated with MBP increases during the hand-grip exercise (r = 0.59, P < 0.01). Plasma catecholamine levels were elevated in both groups of patients (P < 0.025). Plasma adrenaline levels were higher in hypotensive HD patients than in normotensive patients (P < 0.05). alpha 2- and beta 2-adrenoceptor densities and beta 2-adrenoceptor response were reduced in hypotensive patients (P < 0.05 vs normotensive patients). MBP correlated with alpha 2-adrenoceptor (r = 0.46, P < 0.01) and beta 2-adrenoceptor (r = 0.43, P < 0.025) densities in HD patients.
  
  
  CONCLUSIONS
  Normotensive haemodialysed patients have increased plasma catecholamine levels with preserved alpha 2- and beta 2-adrenoceptor numbers, as well as beta 2-adrenoceptor responses. In hypotensive patients, plasma adrenaline levels were even higher; the increased plasma catecholamine levels induced an alpha 2- and beta 2-adrenoceptor downregulation. This downregulation may play a role in the reduced cardiovascular responses to adrenergic stimuli reported in hypotensive HD patients.
authors.affiliation: Nephrology Unit, Hospital Clinic i Provincial, Barcelona, Catalonia, Spain.
authors.forename: N
authors.initials: N
authors.lastname: Esforzado Armengol
authors.forename: A
authors.initials: A
authors.lastname: Cases Amenós
authors.forename: M
authors.initials: M
authors.lastname: Bono Illa
authors.forename: J
authors.initials: J
authors.lastname: Gaya Bertrán
authors.forename: J
authors.initials: J
authors.lastname: Calls Ginesta
authors.forename: F
authors.initials: F
authors.lastname: Rivera Fillat
mesh_terms: D000328:Adult; D001341:Autonomic Nervous System / Q000503:physiopathology*; D016022:Case-Control Studies; D015536:Down-Regulation; D004837:Epinephrine / Q000097:blood; D005260:Female; D006801:Humans; D007022:Hypotension / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology*; D007676:Kidney Failure, Chronic / Q000503:physiopathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D011941:Receptors, Adrenergic / Q000378:metabolism*; D018341:Receptors, Adrenergic, alpha-2 / Q000378:metabolism; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D006435:Renal Dialysis / Q000009:adverse effects*
chemical_list: D011941:Receptors, Adrenergic; D018341:Receptors, Adrenergic, alpha-2; D018343:Receptors, Adrenergic, beta-2; D004837:Epinephrine