Age-dependent decrease in the negative inotropic effect of carbachol on isolated human right atrium

On isolated, electrically driven human right atrial strips, carbachol (10(-8)-10(-3) M) concentration-dependently decreased force of contraction prestimulated with 1 microM forskolin; maximal negative inotropic effects of carbachol (10(-6)-3 x 10(-6) M), however, were in atria from patients aged < 25 years (mean age: 16.8 +/- 2.0 years, n = 9) significantly larger than in patients aged 50-69 years (mean age: 62.5 +/- 0.7 years, n = 33) and were further decreased in patients aged > 70 years (mean age: 73.8 +/- 0.6 years, n = 11). We conclude that, in human right atrium, the recently described age-dependent decrease in muscarinic M2 receptor density is accompanied by a decrease in negative inotropic effects.