ABSTRACT
The spontaneously hypertensive rat (SHR), one of a number of genetically induced models of hypertension, has been used widely for almost three decades as a model for the development of a significant number of cardiovascular drugs used clinically. Drugs that enhance the synaptic levels of brain acetylcholine or directly stimulate cholinergic muscarinic receptors evoke a hypertensive response in several animal species, and in humans. Depletion of neuronal acetylcholine or blockade of central muscarinic receptors in certain brain regions produces a profound fall in blood pressure in the SHR. Five muscarinic receptor genes have been cloned which encode distinct muscarinic cholinergic receptors. Gene products for Ml, M3, and M5 receptors correspond to respective receptors that activate phospholipase C via a pertussis toxin-insensitive G-protein. For collection of all Central Nervous System tissues, animals are sacrificed by rapid decapitation and tissues immediately extracted from the cranium or vertebral column over ice, frozen in liquid nitrogen, and stored at –70°C until assay.
