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Physiol. Genomics 11: 65-72, 2002. First published September 3, 2002; doi:10.1152/physiolgenomics.00079.2002
1094-8341/02 $5.00
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Received 27 June 2002; accepted in final form 21 August 2002.
Physiological Genomics 11:65-72 (2002)
1094-8341/02 $5.00 © 2002 American Physiological Society

Nicotinic receptor gene cluster on rat chromosome 8 in nociceptive and blood pressure hyperresponsiveness

Imran M. Khan 1, Erin Singletary 1, Adamu Alemayehu 1, Shanaka Stanislaus 1, Morton P. Printz 1, Tony L. Yaksh 1,2 and Palmer Taylor 1

1 Department of Pharmacology, University of California, San Diego, California 92093-0636
2 Department of Anesthesiology, University of California, San Diego, California 92093-0636

Spontaneously hypertensive rats (SHR) exhibit enhanced pressor, heart rate, and nociceptive responses to spinal nicotinic agonists. This accompanies a paradoxical decrease in spinal nicotinic receptor number in SHR compared with normotensive rats. The congenic strain, SHR-Lx, with an introgressed chromosome 8 segment from the normotensive Brown-Norway-Lx strain (BN-Lx) exhibits reduced blood pressure. This segment contains a gene cluster for three nicotinic receptor subunits expressed in the nervous system. We examined the implication of this gene cluster in the enhanced responsiveness of the SHR. Pressor and nociceptive responses to spinal cytisine, a nicotinic agonist, were diminished in SHR-Lx. Moreover, with repeated administration, these responses desensitized faster in SHR-Lx and progenitor BN-Lx than in progenitor SHR/Ola. This implicates the gene cluster in both cardiovascular and nociceptive responses to spinal nicotinic agonists. Since diminished responsiveness to agonist stimulation is greater than the basal blood pressure differences between the strains and the introgressed rat chromosome maps to a quantitative trait locus in human hypertension, polymorphisms in the three nicotinic receptor genes become candidates for altered central control of blood pressure.

spinal nicotinic receptor; intrathecal cytisine; spontaneously hypertensive rats; sensory responses; genetics of hypertension




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