Mechanisms involved in the blunted nitric oxide-cGMP pathway in hypertensive TGR(mREN2)27 rats.
In hypertensive TGR(mREN2)27 rats (TGR), the subsensitivity of vascular guanylyl cyclase to nitric oxide could depend on oxidized heme, reduced heme content, or decreased expression of the enzyme. In this study, enzyme activity was stimulated by protoporphyrin-IX, which acts independently of heme, and expression was assessed by Western blot analysis. In TGR aorta, maximum stimulation of soluble guanylyl cyclase by protoporphyrin-IX was 40% lower than in Sprague-Dawley controls, and expression of the beta1-subunit of the enzyme was reduced by 50% (P<0.05, t-test). In conclusion, decreased expression of soluble guanylyl cyclase leads to a blunted response of the nitric oxide-cGMP (guanosine 3',5'-cyclic monophosphate) pathway in TGR aorta.
Jacke
K
K
Faculty of Clinical Medicine, Institute of Pharmacology and Toxicology, Ruprecht-Karls-University Heidelberg, Maybachstrasse 14-16, D-68169 Mannheim, Germany.
Witte
K
K
Lemmer
B
B
D000818:Animals; D030801:Animals, Genetically Modified; D001013:Aorta, Thoracic / Q000187:drug effects / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D006162:Guanylate Cyclase / Q000378:metabolism; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000502:physiology*; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012083:Renin / Q000235:genetics / Q000502:physiology; D015398:Signal Transduction
D011524:Protoporphyrins; D009569:Nitric Oxide; C028025:protoporphyrin IX; D012083:Renin; D006162:Guanylate Cyclase; D006152:Cyclic GMP