The association of
histamine with adverse cardiac remodeling in chronic pressure overload has not received much attention. A pilot study in spontaneously hypertensive rats (SHRs) indicated a reduction of
left ventricular hypertrophy (LVH) with a histamine-2-receptor (H2R) antagonist (
famotidine). This finding prompted a detailed investigation of temporal variation in myocardial
histamine and H2R expression and the cardiovascular response to H2R antagonism compared with that of the conventional beta-blocker
metoprolol. Reduction of LVH is known to reduce the risk of adverse cardiovascular events. The myocardial
histamine content and H2R expression increased with age in SHRs but not in normotensive Wistar rats. The cardiovascular response to
famotidine (30 mg kg-1) was compared with that of
metoprolol (50 mg kg-1) in 6-month-old male SHRs treated for 60 days. The decrease in diastolic blood pressure and improvement in cardiac function induced by
famotidine and
metoprolol were comparable. Both treatments caused the regression of LVH as assessed from the
hypertrophy index, histomorphometry,
B type natriuretic peptide (BNP), pro-
collagen 1, and
hydroxyproline levels.
Calcineurin-A expression (marker of pathological remodeling) decreased, and Peroxiredoxin-3 expression (mitochondrial
antioxidant) increased in response to the treatments. The myocardial
histamine levels decreased with the treatments. The age-dependent increase in myocardial
histamine and H2R in the SHRs signifies their association with progressive cardiac remodeling. The regression of LVH and improvement in cardiac function by
famotidine further demonstrates the role of
histamine in cardiac remodeling.
Hypertrophy of cultured cardiac cells upon exposure to
histamine and the H2R agonist
amthamine substantiates the role of
histamine in cardiac remodeling. The cardiovascular response to
famotidine is comparable to that of
metoprolol, suggesting repurposing of H2R antagonists for the management of hypertensive
heart disease.