EFFECTS OF GROWTH-RATE AND CELL-DENSITY ON NERVE GROWTH-FACTOR SECRETION IN CULTURES OF VASCULAR AND BLADDER SMOOTH-MUSCLE CELLS FROM HYPERTENSIVE AND HYPERACTIVE RATS

Elevated target-derived smooth muscle nerve growth factor (NGF) and re sultant neurogenic plasticity are associated with both hypertension an d hyperactive voiding in spontaneously hypertensive rats (SHRs: hypert ensive, behaviorally hyperactive). In culture, vascular (VSMCs) and bl adder (BSMCs) smooth muscle cells derived from SHRs secrete higher lev els of NGF, proliferate more rapidly, and achieve higher density at co nfluence than do control Wistar-Kyoto (WKY) cells. To elucidate growth -related contributions to the elevated tissue NGF observed in SHRs, we examined vascular VSMC and BSMC NGF secretion in two inbred cell line s (WKHTs, hypertensive; WKHAs, hyperactive) derived from SHRs and WKYs to assess the phenotypic association of altered NGF metabolism with e ither hypertension or behavioral hyperactivity. Cell density, rather t han growth rates, was the most important factor with respect to NGF se cretion. VSMC density varied such that WKHT=SHR>WKY= WKHA, higher VSMC density being associated with higher NGF output. However, in BSMC cul tures, NGF output was the lowest in high density cell lines, with WKHT >SHR>WKY>WKHA. SHR BSMCs had the second highest cell density and NGF s ecretion level. Elevated packing density, presumably because of a lack of contact inhibition, co-segregated with the hypertensive phenotype in both VSMCs and BSMCs. Thus, dysfunctional smooth muscle growth char acteristics may contribute to the augmented vascular and bladder NGF c ontent associated with high blood pressure and hyperactive voiding in SHRs.