Species variability in angiotensin receptor expression by cultured cardiac fibroblasts and the infarcted heart

Abstract

Cardiac fibroblasts, an abundant cell of the left ventricle (LV), proliferate and synthesize collagen in the heart after acute injury and during pressure overload hypertrophy. From many studies, angiotensin II (ANG II) receptors have been implicated in promoting collagen formation by the rat cardiac fibroblast. The present study examined species variability in ANG II receptor expression. Cultured rat fibroblasts expressed 43,000 ± 15,000 ANG II (AT1-specific) receptors per cell (dissociation constant = 0.92 ± 0.34 nM), whereas rabbit and neonate human cardiac fibroblast cultures expressed few receptors. Angiotensin increased intracellular Ca2+ concentration in rats but not in rabbit or human cardiac fibroblasts and stimulated arachidonic acid release in rat but not rabbit fibroblasts. In situ, 6 days after coronary artery ligation, angiotensin receptor expression was increased 34.8 ± 13.4-fold in the infarcted area relative to the noninfarcted tissue in the rat LV, whereas rabbit hearts demonstrated only a 3.2 ± 1.6-fold increase in ANG II binding within the infarcted tissue. These species differences in receptor expression raise questions as to the role of angiotensin as a mediator of collagen formation across species and as a direct target of angiotensin-converting enzyme inhibitors to regulate cardiac fibroblast function.