Abstract
Hypertension, a major comorbidity in patients with heart failure with preserved ejection
fraction, is associated with cardiac remodelling, dysfunction, and altered calcium
homeostasis. However, existing models of study and evidence on the mechanisms driving
this form of cardiomyopathy remain contradictory. This study aimed to establish a relevant hypertensive model and to assess alterations in the expression and activation of
calcium handling proteins. Mini pumps containing either saline as a vehicle control or
Angiotensin II (Ang II) were surgically implanted into adult male Sprague–Dawley rats for
4 weeks. Body weight and tail-cuff-derived blood pressure measurements were recorded
pre-surgery and 1 week and 4 weeks post-surgery. Following treatment, cardiac function
was assessed, body and organ measurements were obtained, and cardiac tissue was processed for biochemical analysis. Rats infused with Ang II exhibited an increased heart
weight to body weight ratio, evidencing cardiac hypertrophy (control: 0.00342, n = 4; Ang
II: 0.00407, n = 6). Blood pressure was significantly enhanced even at 1 week post-treatment
(control: 119 mmHg, n = 4; Ang II: 178 mmHg, n = 6). Furthermore, echocardiographic
analysis revealed a mild increase in left ventricular contractility (control: 50.57%, n = 8;
Ang II: 55.98%, n = 12). Initial biochemical analysis revealed no change in Phospholamban
phosphorylation (control: 1.00, n = 8; Ang II: 1.13, n = 12). Also, data revealed an increase
in the phosphorylation of the Ryanodine receptor via the calcium-calmodulin-dependent
protein kinase II (CaMKII) site (control: 1.00, n = 6; Ang II: 2.49, n = 8), coupled with
a trend towards increased CaMKII oxidation (control: 1.00, n = 7; Ang II: 2.33, n = 11;
p = 0.0552). These findings evidence that Ang II induced both cardiac hypertrophy and
hypertension in vivo. Additionally, ongoing biochemical evaluation suggests a role of
CaMKII in mediating these modifications.
fraction, is associated with cardiac remodelling, dysfunction, and altered calcium
homeostasis. However, existing models of study and evidence on the mechanisms driving
this form of cardiomyopathy remain contradictory. This study aimed to establish a relevant hypertensive model and to assess alterations in the expression and activation of
calcium handling proteins. Mini pumps containing either saline as a vehicle control or
Angiotensin II (Ang II) were surgically implanted into adult male Sprague–Dawley rats for
4 weeks. Body weight and tail-cuff-derived blood pressure measurements were recorded
pre-surgery and 1 week and 4 weeks post-surgery. Following treatment, cardiac function
was assessed, body and organ measurements were obtained, and cardiac tissue was processed for biochemical analysis. Rats infused with Ang II exhibited an increased heart
weight to body weight ratio, evidencing cardiac hypertrophy (control: 0.00342, n = 4; Ang
II: 0.00407, n = 6). Blood pressure was significantly enhanced even at 1 week post-treatment
(control: 119 mmHg, n = 4; Ang II: 178 mmHg, n = 6). Furthermore, echocardiographic
analysis revealed a mild increase in left ventricular contractility (control: 50.57%, n = 8;
Ang II: 55.98%, n = 12). Initial biochemical analysis revealed no change in Phospholamban
phosphorylation (control: 1.00, n = 8; Ang II: 1.13, n = 12). Also, data revealed an increase
in the phosphorylation of the Ryanodine receptor via the calcium-calmodulin-dependent
protein kinase II (CaMKII) site (control: 1.00, n = 6; Ang II: 2.49, n = 8), coupled with
a trend towards increased CaMKII oxidation (control: 1.00, n = 7; Ang II: 2.33, n = 11;
p = 0.0552). These findings evidence that Ang II induced both cardiac hypertrophy and
hypertension in vivo. Additionally, ongoing biochemical evaluation suggests a role of
CaMKII in mediating these modifications.
| Original language | English |
|---|---|
| Article number | 2.27 |
| Journal | Medical Science Forum |
| Volume | 27 |
| Issue number | (1) 3 |
| DOIs | |
| Publication status | Published - 28 Aug 2024 |