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(Circulation Research. 1995;76:142-147.)
© 1995 American Heart Association, Inc.

Articles

Alterations in the Expression of the Genes Encoding Specific Muscarinic Receptor Subtypes in the Hypothalamus of Spontaneously Hypertensive Rats

Jian Wei, Antonio Milici, Jerry J. Buccafusco

From the Department of Pharmacology and Toxicology (J.J.B.) and the Department of Psychiatry and Health Behavior, Medical College of Georgia, Augusta, and the Department of Veterans Affairs Medical Center, Augusta, Ga.

Correspondence to Dr Jerry J. Buccafusco, Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta, GA 30912-2300.

Abstract A significant body of evidence exists that is consistent with the possibility that heightened cholinergic activity in certain brain regions, such as the hypothalamus, leads to increased sympathetic tone and subsequent hypertension. The increase in cholinergic activity is mediated at least in part through enhanced sensitivity of muscarinic receptors. In this study, we used the technique of reverse transcriptase–polymerase chain reaction to estimate the relative levels of mRNA encoding the five known subtypes of muscarinic receptors within the hypothalamus of spontaneously hypertensive rats (SHR), a genetic model of the disease, and their normotensive counterparts (Wistar-Kyoto rats). SHR exhibited a significant increase (40% to 50%) in the excitatory M1 subtype (confirmed by receptor binding) and a decrease in the inhibitory M4 subtype of muscarinic receptors before and during the establishment of hypertension. Such alterations may form part of the genotypic profile of inherited hypertension.

Key Words: muscarinic receptors • spontaneously hypertensive rats • transcription • blood pressure • hypothalamus

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