Abnormality of calmodulin activity in hypertension. Evidence of the presence of an activator.
An apparent increase of calmodulin (CaM) activity was previously observed in the heart and kidney but not in the liver of spontaneously-hypertensive rats (SHR) and mice compared with their corresponding normotensive controls. As this change was due to an elevated recovery of CaM in the organs of the hypertensive animals, the present study was designed to evaluate its activity in hypertension. A CaM activator, detected in heart and kidney supernatants from hypertensive animals, was found to be responsible for this enhanced recovery. Similar results were obtained with passaged, cultured aortic smooth muscle cells from SHR, indicating that the anomaly was not a mere consequence of elevated blood pressure but rather a genetic expression of cells of hypertensive origin. The activator was heat stable, nondialyzable, and recovered in the fraction precipitated with 30-50% ammonium sulfate. Preliminary extraction studies suggest that the activator is contained in a glycolipid fraction. The stimulation of phosphodiesterase by this activator was calcium and CaM dependent. The activator appears to affect the affinity of the phosphodiesterase for CaM rather than the maximal stimulation. The activator was also present at a low concentration in the heart and kidney of normotensive animals. These findings indicate that at least some of the calcium abnormalities implicated in the pathogenesis of hypertension could be the result of interactions between CaM, calcium, and this activator.
Huang
S L
SL
Clinical Research Institute of Montreal, Quebec, Canada.
Wen
Y I
YI
Kupranycz
D B
DB
Pang
S C
SC
Schlager
G
G
Hamet
P
P
Tremblay
J
J
D000818:Animals; D002118:Calcium / Q000502:physiology; D002147:Calmodulin / Q000302:isolation & purification / Q000502:physiology*; D002474:Cell-Free System; D005591:Chemical Fractionation; D004789:Enzyme Activation; D004986:Ether; D006973:Hypertension / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology; D007668:Kidney / Q000378:metabolism; D008297:Male; D051379:Mice; D009131:Muscle, Smooth, Vascular / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D010727:Phosphoric Diester Hydrolases / Q000378:metabolism; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014020:Tissue Extracts / Q000032:analysis
D002147:Calmodulin; D014020:Tissue Extracts; D004986:Ether; D010727:Phosphoric Diester Hydrolases; D002118:Calcium