title: Relevance of plasma noradrenaline concentrations to estimate autonomic effects of antihypertensive drugs.
abstract: The sympathetic nervous system is important in regulating cardiovascular function. It is therefore of interest to study the influence of antihypertensive drugs on sympathetic nerve activity. For this purpose, measurements of noradrenaline concentrations in forearm venous plasma have often been used. For several reasons, this provides limited information: i) the sympathetic nervous system is highly differentiated, i.e. activity may be high in some organs and low in others; ii) noradrenaline in forearm venous plasma is largely derived from sympathetic activity to the forearm skeletal muscle; iii) plasma noradrenaline concentrations are determined not only by noradrenaline spillover from sympathetic nerve endings, which is related to sympathetic nerve activity, but also by noradrenaline clearance. Under most circumstances plasma noradrenaline concentrations are not high enough to produce hormonal effects. Many types of antihypertensive drugs may cause acute and long-term increases in forearm venous noradrenaline concentrations. The mechanisms underlying these increases are not fully understood but seem to differ between drug classes: Diuretics increase renal noradrenaline spillover; beta-blockers do not affect spillover but reduce total noradrenaline clearance; calcium antagonists and alpha-blockers probably increase noradrenaline spillover, but it is not known which organs are involved, particularly during long-term treatment. ACE inhibitors seem to have a sympatholytic action, which counteract reflex increases in sympathetic nerve activity during blood pressure reduction, and plasma noradrenaline concentrations are generally not affected. To be able to judge the possible clinical consequences of changes in plasma noradrenaline concentrations during chronic antihypertensive treatment, assessments of noradrenaline spillover from individual organs are needed.
authors.affiliation: Astra Hässle AB, Mölndal, Sweden.
authors.forename: D
authors.initials: D
authors.lastname: Elmfeldt
authors.forename: L
authors.initials: L
authors.lastname: Elvelin
authors.forename: M
authors.initials: M
authors.lastname: Nordlander
mesh_terms: D000959:Antihypertensive Agents / Q000145:classification / Q000494:pharmacology* / Q000627:therapeutic use; D016477:Artifacts; D001794:Blood Pressure / Q000502:physiology; D004341:Drug Evaluation; D005542:Forearm / Q000098:blood supply; D006207:Half-Life; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D009132:Muscles / Q000098:blood supply; D009638:Norepinephrine / Q000097:blood* / Q000378:metabolism; D009928:Organ Specificity; D013315:Stress, Psychological / Q000097:blood; D013564:Sympathetic Nervous System / Q000503:physiopathology
chemical_list: D000959:Antihypertensive Agents; D009638:Norepinephrine