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Acetylcholine regulates perfusion of numerous organs via changes in local blood flow involving muscarinic receptor-induced release of vasorelaxing agents from the endothelium. The purpose of the present study was to determine the role of M1, M3, and M5 muscarinic acetylcholine receptors in vasodilation of small arteries using gene-targeted mice deficient in either of the three receptor subtypes (M1R−/−, M3R−/−, or M5R−/− mice, respectively). Muscarinic receptor gene expression was determined in murine cutaneous, skeletal muscle, and renal interlobar arteries using real-time PCR. Moreover, respective arteries from M1R−/−, M3R−/−, M5R−/−, and wild-type mice were isolated, cannulated with micropipettes, and pressurized. Luminal diameter was measured using video microscopy. mRNA for all five muscarinic receptor subtypes was detected in all three vascular preparations from wild-type mice. However, M3 receptor mRNA was found to be most abundant. Acetylcholine produced dose-dependent dilation in all three vascular preparations from M1R−/−, M5R−/−, and wild-type mice. In contrast, cholinergic dilation was virtually abolished in arteries from M3R−/− mice. Deletion of either M1, M3, or M5 receptor genes did not affect responses to nonmuscarinic vasodilators, such as substance P and nitroprusside. These findings provide the first direct evidence that M3 receptors mediate cholinergic vasodilation in cutaneous, skeletal muscle, and renal interlobar arteries. In contrast, neither M1 nor M5 receptors appear to be involved in cholinergic responses of the three vascular preparations tested.

A model for parathyroid gland response to an epinephrine infusion is proposed. It is based on direct measurements of the parathyroid hormone (PTH) secretion rate as measured directly after cannulation of the venous drainage of single superior parathyroid glands of calves. When epinephrine was infused into a jugular vein, a large increase of PTH secretion rate was observed at the beginning of the infusion. The PTH secretion rate thereafter fell, but it was still significantly above the control rate. At the end of the epinephrine infusion a sharp decrease was observed when the infusion was terminated. These observations are consistent with a rate-sensitive control mechanism. Calculation of the parameters yielded a model, which was then linked with a kinetic model for PTH distribution. Simulation studies were undertaken to predict plasma PTH concentration in response to an epinephrine infusion. Good agreement was found between predicted results and previously published work. The role of this rate-sensitive mechanism in the parathyroid gland is discussed.