Hypercholesterolemia and hypertension have synergistic deleterious effects on coronary endothelial function.
OBJECTIVE
Coronary endothelial dysfunction is associated with an increase in cardiac events. Hypercholesterolemia (HC) and hypertension (HT) are both associated with endothelial dysfunction, and their coexistence is associated with an increased incidence of cardiac events in epidemiological studies. However, pathogenic mechanisms are poorly understood. Here we studied the effects of coexisting HC and HT on coronary endothelial function.


RESULTS
Four groups of pigs were studied after 12 weeks of a normal diet (n=9), a 2% HC diet (n=9), HT (achieved by unilateral renal artery stenosis, n=8), or HC+HT (n=6). Coronary endothelial function was tested, in epicardial arteries and arterioles, by using organ chamber techniques. Oxidative stress was measured in coronary artery tissue. Vasodilatory response to bradykinin and calcium ionophore was significantly impaired in animals with HC+HT compared with each risk factor alone (P<0.05 for both). In animals with coexistent HC and HT, the increase in oxidative stress was more pronounced compared with each risk factor alone (P<0.05). Furthermore, chronic antioxidant supplementation significantly improved coronary artery vasoreactivity.


CONCLUSIONS
These results suggest that HC and HT have a synergistic deleterious effect on coronary endothelial function, associated with increased oxidative stress. This interaction may contribute to the increased incidence of coronary heart disease and cardiac events seen when HC and HT coexist.
Rodriguez-Porcel
Martin
M
Department of Internal Medicine, Division of Cardiovascular Diseases, Mayo Clinic, 200 First St SW, Rochester, Minn 55905, USA.
Lerman
Lilach O
LO
Herrmann
Joerg
J
Sawamura
Tatsuya
T
Napoli
Claudio
C
Lerman
Amir
A
D000818:Animals; D000975:Antioxidants / Q000627:therapeutic use; D001205:Ascorbic Acid / Q000627:therapeutic use; D001920:Bradykinin / Q000494:pharmacology; D000001:Calcimycin / Q000494:pharmacology; D003324:Coronary Artery Disease / Q000097:blood / Q000209:etiology* / Q000503:physiopathology; D003331:Coronary Vessels / Q000201:enzymology / Q000473:pathology*; D006152:Cyclic GMP / Q000096:biosynthesis; D004036:Diet, Atherogenic; D019332:Endothelin-1 / Q000494:pharmacology; D004730:Endothelium, Vascular / Q000187:drug effects / Q000503:physiopathology*; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications*; D006978:Hypertension, Renovascular / Q000097:blood / Q000150:complications*; D008055:Lipids / Q000097:blood; D009569:Nitric Oxide / Q000378:metabolism; D009599:Nitroprusside / Q000494:pharmacology; D018384:Oxidative Stress; D012078:Renal Artery Obstruction / Q000097:blood / Q000150:complications; D012083:Renin / Q000097:blood; D013373:Substance P / Q000494:pharmacology; D013552:Swine; D014665:Vasodilator Agents / Q000494:pharmacology; D014810:Vitamin E / Q000627:therapeutic use
D000975:Antioxidants; D019332:Endothelin-1; D008055:Lipids; D014665:Vasodilator Agents; D014810:Vitamin E; D009599:Nitroprusside; D009569:Nitric Oxide; D013373:Substance P; D000001:Calcimycin; D012083:Renin; D006152:Cyclic GMP; D001205:Ascorbic Acid; D001920:Bradykinin