Protein kinase C isozymes in hypertension and hypertrophy: insight from SHHF rat hearts.
Chronic hypertension results in cardiac hypertrophy and may lead to congestive heart failure. The protein kinase C (PKC) family has been identified as a signaling component promoting cardiac hypertrophy. We hypothesized that PKC activation may play a role mediating hypertrophy in the spontaneously hypertensive heart failure (SHHF) rat heart. Six-month-old SHHF and normotensive control Wistar Furth (WF) rats were used. Hypertension and cardiac hypertrophy were confirmed in SHHF rats. PKC expression and activation were analyzed by Western blots using isozyme-specific antibodies. Compared to WF, untreated SHHF rats had increased phospho-active alpha (10-fold), delta (4-fold), and epsilon (3-fold) isozyme expression. Furthermore, we analyzed the effect of an angiotensin II type 1 receptor blocker (ARB) and hydralazine (Hy) on PKC regulation in SHHF rat left ventricle (LV). Both the ARB and Hy normalized LV blood pressure, but only the ARB reduced heart mass. Neither treatment affected PKC expression or activity. Our data show differential activation of PKC in the hypertensive, hypertrophic SHHF rat heart. Regression of hypertrophy elicited by an ARB in this model occurred independently of changes in the expression and activity of the PKC isoforms examined.
Johnsen
Dustin D
DD
Cardiovascular Research Institute, University of South Dakota and Sioux Valley Hospital and Health Systems, Sioux Falls, South Dakota 57105, USA.
Kacimi
Rachid
R
Anderson
Brent E
BE
Thomas
Tracy A
TA
Said
Suleman
S
Gerdes
A Martin
AM
D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology; D000818:Animals; D015153:Blotting, Western; D004789:Enzyme Activation; D005260:Female; D006321:Heart / Q000502:physiology*; D006352:Heart Ventricles / Q000378:metabolism; D006830:Hydralazine / Q000494:pharmacology; D006973:Hypertension / Q000201:enzymology*; D006984:Hypertrophy / Q000201:enzymology*; D009206:Myocardium / Q000201:enzymology* / Q000473:pathology; D010766:Phosphorylation; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000096:biosynthesis / Q000737:chemistry*; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon; D051381:Rats; D011918:Rats, Inbred SHR; D011920:Rats, Inbred WF; D015398:Signal Transduction
D047228:Angiotensin II Type 1 Receptor Blockers; D020033:Protein Isoforms; D006830:Hydralazine; C497260:Prkcd protein, rat; C497257:Prkce protein, rat; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha; D051745:Protein Kinase C-delta; D051744:Protein Kinase C-epsilon