The
renin-angiotensin and
sympathetic nervous systems play critical interlinked roles in the development of
left ventricular hypertrophy,
fibrosis, and dysfunction. These studies investigated the
hemodynamic and
cardiac effects of monoblockade and coblockade of
renin-angiotensin and
sympathetic nervous systems. Stroke-prone spontaneously
hypertensive rats (16 weeks old; male; n=12 per group) received the
sympatholytic imidazoline compound,
moxonidine (2.4 mg/kg per day); the
angiotensin-receptor blocker eprosartan (30 mg/kg per day), separately or in combination; or saline vehicle for 8 weeks, SC, via
osmotic minipumps.
Blood pressure and
heart rate were continuously measured by radiotelemetry. After 8 weeks, in vivo
cardiac function and structure were measured by
transthoracic echocardiography and a Millar conductance catheter, and the rats were then
euthanized and
blood and
heart ventricles collected for various determinations. Compared with vehicle, the subhypotensive dose of
moxonidine resulted in lower (P<0.01)
heart rate,
left ventricular hypertrophy,
cardiomyocyte cross-sectional area,
interleukin 1 beta,
tumor necrosis factor-alpha, and
mRNA for natriuretic
peptides.
Eprosartan reduced pressure (P<0.01), as well as
extracellular signal-regulated kinase (ERK) 44
phosphorylation, Bax/
Bcl-2, and
collagen I/III, and improved
left ventricular diastolic function (P<0.03). Combined treatment resulted in greater reductions in
blood pressure,
heart rate,
left ventricular hypertrophy,
collagen I/III, and inhibited inducible
NO synthase and increased
endothelial NO synthase phosphorylation, as well as reduced
left ventricular anterior wall thickness, without altering the other parameters. Thus, in advanced
hypertension complicated with
cardiac fibrosis,
sympathetic inhibition and
angiotensin II blockade resulted in greater reduction in
blood pressure and
heart rate, inhibition of
inflammation, and improved
left ventricular pathology but did not add to the benefits of
angiotensin II blockade on
cardiac function.
