The effect of hypercholesterolemia on platelet soluble guanylyl cyclase.
We sought to determine whether hypercholesterolemia impacts on the NO-stimulated activity of platelet soluble guanylyl cyclase (sGC). We investigated two groups of nine New Zealand white rabbits receiving either a standard (NC) or a cholesterol chow (HC, 0.75%) for 15 weeks. The plasma content of cGMP and the specific activity of sGC in intact platelets were measured by a cGMP-specific radioimmunoassay. In HC, 47.9+/-3.1% of the aortic intimal area was covered with atherosclerotic lesions, and plasma cGMP levels (pmol/ml) were increased from 12.6+/-1.2 to 27.9+/-3.5 (P<.0001). In striking contrast, hypercholesterolemia had no effect on sGC activity stimulated by the NO donor SNAP. At 100 microM SNAP, the specific activities of sGC (pmol/10(9) platelets/min) were 81.8+/-14.5 in NC and 86.2+/-8.1 in HC. Basal sGC activity (pmol/10(9) platelets/min) was also similar in NC (0.21+/-0.04) and HC (0.460+/-0.11, P=.7813). In accordance, washed platelets from both groups showed a similar SNAP-induced inhibition of aggregation. These data suggest that an impaired response of platelets to NO is most likely not involved in platelet hyperreactivity in hypercholesterolemia.
D000818:Animals; D001012:Aorta, Abdominal / Q000473:pathology; D001013:Aorta, Thoracic / Q000473:pathology; D001161:Arteriosclerosis / Q000097:blood / Q000209:etiology / Q000473:pathology; D001792:Blood Platelets / Q000201:enzymology* / Q000473:pathology; D006152:Cyclic GMP / Q000097:blood; D006162:Guanylate Cyclase; D006937:Hypercholesterolemia / Q000097:blood / Q000150:complications / Q000201:enzymology*; D009569:Nitric Oxide / Q000378:metabolism; D020030:Nitric Oxide Donors / Q000494:pharmacology; D010396:Penicillamine / Q000031:analogs & derivatives* / Q000494:pharmacology; D010974:Platelet Aggregation; D010976:Platelet Count; D011817:Rabbits; D018160:Receptors, Cytoplasmic and Nuclear / Q000378:metabolism*; D012995:Solubility; D000071756:Soluble Guanylyl Cyclase; D017539:Tunica Intima / Q000473:pathology
D020030:Nitric Oxide Donors; D018160:Receptors, Cytoplasmic and Nuclear; C110881:S-nitro-N-acetylpenicillamine; D009569:Nitric Oxide; D006162:Guanylate Cyclase; D000071756:Soluble Guanylyl Cyclase; D010396:Penicillamine; D006152:Cyclic GMP