Effects of hydrochlorothiazide and propranolol treatment on chylomicron metabolism in hypertensive objects.
Modifications in chylomicron metabolism caused by antihypertensive drugs were investigated in hypertensive subjects because previous studies had indicated that diuretics and beta-blockers modify the plasma lipid concentrations through mechanisms that were not fully understood. A triglyceride-rich emulsion resembling lymph chylomicrons, labeled with (3H) triolein and (14C) cholesteryl oleate, was infused intravenously into mildly hypertensive patients after 8 weeks on placebo and subsequently on hydrochlorothiazide (n = 10) or propranolol (n = 8). The residence time of both radioactivities in plasma was utilized for the simultaneous calculation of the particle remnant removal rate and of the lipoprotein lipase activity expressed as a delipidation index = 1 - [(3H) triolein residence time/(14C) cholesteryl oleate residence time]. Treatment with hydrochlorothiazide diminished the delipidation rate value whereas propranolol mildly increased the removal rate of the remnant particle. These alterations of the chylomicron kinetics were not accompanied by changes in plasma triglycerides, glucose, and insulin concentration as measured in the fasting state. The impairment of the lipoprotein lipase activity by thiazides and the faster removal rate of the whole particle by propranolol could explain the reason why in previous clinical studies the simultaneous use of these drugs does not aggravate the hyperlipidemia known to be induced by thiazides alone.
Bernik
Márcia M S
MM
Lipids Laboratory (LIM 10), s/3317, Endocrinology Section, Department of Internal Medicine, University of São Paulo Medical School, Av. Dr. Arnaldo 455, CEP 01246-903 São Paulo, Brazil.
Heimann
Joel C
JC
Nakandakare
Edna R
ER
Cazita
Patrícia M
PM
Nunes
Valéria S
VS
Rocha
Jussara C
JC
Neves
Mônica Q T S
MQ
Quintão
Eder C R
EC
D000328:Adult; D000368:Aged; D000959:Antihypertensive Agents / Q000627:therapeutic use*; D002788:Cholesterol Esters / Q000378:metabolism / Q000493:pharmacokinetics; D002914:Chylomicrons / Q000378:metabolism*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D006801:Humans; D006852:Hydrochlorothiazide / Q000627:therapeutic use*; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism* / Q000503:physiopathology; D008055:Lipids / Q000097:blood; D008079:Lipoproteins, VLDL / Q000097:blood; D008297:Male; D008875:Middle Aged; D011433:Propranolol / Q000627:therapeutic use*; D014304:Triolein / Q000378:metabolism / Q000493:pharmacokinetics
D000959:Antihypertensive Agents; D002788:Cholesterol Esters; D002914:Chylomicrons; D008055:Lipids; D008079:Lipoproteins, VLDL; D006852:Hydrochlorothiazide; D014304:Triolein; C014409:cholesteryl oleate; D011433:Propranolol