Norepinephrine-related mechanism in hypertension accompanying renal failure.
Various blood pressure (BP)-regulating factors were assessed before and after 4 weeks of selective norepinephrine (NE) inhibition with the sympathetic neurone blocker, debrisoquine, in nine hypertensive, nine normotensive hemodialysis patients (HDP), and 11 normal subjects. On placebo, hypertensive HDP had an increased total blood volume (P less than 0.05) and exchangeable sodium (P less than 0.001), while both HDP groups had increased (P less than 0.05) plasma clearances of NE and angiotensin II (AII), and tended to have higher basal plasma NE, renin, and AII levels, and lower BP responses to NE or AII than normal subjects. Plasma epinephrine and the chronotropic dose of isoproterenol (CDI) did not differ significantly among groups. Debrisoquine lowered supine BP markedly in hypertensive HDP (on average from 181/107 to 148/88 mm Hg) and slightly in normotensive HDP (143/78 to 131/76 mm Hg), but not in normal subjects (116/74 to 120/79 mm Hg). In all groups, plasma NE, CDI, and NE pressor dose were reduced in parallel (by 35 to 75%; P less than 0.05 to less than 0.001), and the relation between stepwise increasing plasma NE and BP changes during NE infusion was commensurably displaced to the left (P less than 0.01). The remaining parameters were not changed consistently.


CONCLUSIONS
HDP, as normal subjects, respond to decreased sympathetic outflow with increased alpha- and beta-receptor sensitivity. Hypertension in HDP depends strongly on a NE-related mechanism. The latter seems to complement renin-angiotensin, sodium and fluid volume in the pathogenesis of high BP.
D000328:Adult; D000368:Aged; D000804:Angiotensin II; D001794:Blood Pressure; D001810:Blood Volume; D003647:Debrisoquin; D005260:Female; D006339:Heart Rate; D006801:Humans; D006973:Hypertension / Q000209:etiology*; D007545:Isoproterenol; D007676:Kidney Failure, Chronic / Q000150:complications* / Q000503:physiopathology / Q000628:therapy; D008297:Male; D008875:Middle Aged; D009638:Norepinephrine / Q000502:physiology*; D006435:Renal Dialysis
D000804:Angiotensin II; D007545:Isoproterenol; D003647:Debrisoquin; D009638:Norepinephrine