Nicotinic receptor gene cluster on rat chromosome 8 in nociceptive and blood pressure hyperresponsiveness.
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.
Khan
Imran M
IM
Department of Pharmacology, University of California, San Diego, California 92093-0636, USA. ikhan@ucsd.edu
Singletary
Erin
E
Alemayehu
Adamu
A
Stanislaus
Shanaka
S
Printz
Morton P
MP
Yaksh
Tony L
TL
Taylor
Palmer
P
D000470:Alkaloids / Q000008:administration & dosage / Q000378:metabolism; D000818:Animals; D020296:Animals, Congenic; D001392:Azocines; D001794:Blood Pressure / Q000187:drug effects* / Q000235:genetics*; D002875:Chromosomes / Q000235:genetics*; D004334:Drug Administration Schedule; D004361:Drug Tolerance / Q000502:physiology; D005260:Female; D006339:Heart Rate / Q000187:drug effects / Q000235:genetics; D006973:Hypertension / Q000235:genetics*; D007278:Injections, Spinal; D008297:Male; D005810:Multigene Family / Q000235:genetics*; D018722:Nicotinic Agonists / Q000008:administration & dosage / Q000378:metabolism; D011807:Quinolizines; D051381:Rats; D011914:Rats, Inbred BN; D011918:Rats, Inbred SHR; D011978:Receptors, Nicotinic / Q000235:genetics*; D013127:Spinal Nerves / Q000737:chemistry / Q000187:drug effects; D013623:Tail / Q000098:blood supply; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D001392:Azocines; D018722:Nicotinic Agonists; D011807:Quinolizines; D011978:Receptors, Nicotinic; C004712:cytisine; D000093843:Quinolizidine Alkaloids