Contraction of Cultured Rat Glomerular Cells of Apparent Mesangial Origin after Stimulation with Angiotensin II and Arginine Vasopressin

Abstract

Studies to identify the physiological role of glomerular mesangial cells were undertaken using homogeneous cultures of rat glomerular cells of apparent mesangial origin (MS). Cultured MS cells were treated with arginine vasopressin (AVP), angiotensin II (AGII), prostaglandin E₂, and parathyroid hormone. AVP (0.1 nM) and AGII (1 nM) stimulated contraction of MS cells in vitro that was complete by 2 min at 37°C or 10 min at 23°C as observed by phase contrast and electron microscopy. Relaxation recurred 15 min after hormonal addition at 23°C. Similar experiments in cloned rat glomerular epithelial cells or “renin”-producing cells did not demonstrate a contractile response. The contraction of MS cells was independent of cyclic AMP (cAMP) and cyclic 3′,5′-guanosine monophosphate (cGMP) production, even when cyclic nucleotides were measured as early as 30 s after hormonal stimulation. To demonstrate that contraction was a function of hormone-receptor interaction, binding of [³H](8-lysine)vasopressin was studied. Specific binding for 1.6 and 5 nM hormone was both time- and dose-dependent. The estimated apparent affinity was 10 nM. In late MS cell passages (>16th) that no longer demonstrated hormone-stimulated contraction, no specific binding of [³H](8-lysine)vasopressin was observed. Incubations were modified to optimize the conditions for detecting the effect of hormones on cell cyclic nucleotide content. A supramaximal concentration of AVP (200 nM) increased the cAMP content of MS cells twofold in the presence of a phosphodiesterase inhibitor. Similar experiments with prostaglandin E₂ (1 μg/ml) led to a 1.5-6-fold increase in MS cell cAMP content, but no effect on contraction was observed. Neither hormone altered cGMP content. These data are further support for the independence of contraction and cyclic nucleotide production. Our studies suggest that MS cells are the equivalent of smooth muscle cells in the glomerulus and that their contraction may be important in control of glomerular filtration.