Possible biochemical mechanisms involved in the antihypertensive drug-induced changes in serum lipoproteins.
The antihypertensive drug-induced changes in serum lipoproteins can be attributed to two major mechanisms, namely an increased hepatic lipoprotein synthesis and a disturbed lipoprotein catabolism. Thiazides, by inhibiting phosphodiesterase, increase the intracellular concentration of cyclic AMP leading to a stimulation of lipolysis. beta-Blockers may reduce the adenylate cyclase activity in liver cells, leading to a reduced inhibition of the liver triglyceride synthesis and a higher secretion of VLDL triglyceride particles. alpha-Blockade through phosphodiesterase inhibition and an increased cAMP level, can result in a blockade of the liver triglyceride synthesis and a reduced serum triglyceride concentration. Lipoprotein lipase activity is reduced by beta-blockers and stimulated by alpha-blockers, leading, respectively, to a lower and a higher plasma HDL cholesterol. Besides these two major mechanisms, a direct effect of antihypertensive drugs on intracellular cholesterol synthesis can also be postulated.
Lijnen
P
P
Hypertension and Cardiovascular Rehabilitation Unit, Department of Pathophysiology, K.U. Leuven, Belgium.
Fagard
R
R
Staessen
J
J
Amery
A
A
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D006801:Humans; D008074:Lipoproteins / Q000097:blood*
D000959:Antihypertensive Agents; D008074:Lipoproteins