Augmented responses to intrathecal nicotinic agonists in spontaneous hypertension.
Abnormal central cholinergic activity has been reported to be responsible in part for the pathogenesis of high blood pressure in spontaneously hypertensive rats (SHR). Administration of cholinergic agonists in brain and spinal cord results in exaggerated pressor responses in SHR. Studies to date have focused largely on the muscarinic cholinergic system. Recently, we demonstrated that intrathecal administration of nicotinic agonists results in pressor, tachycardic, and irritation responses. In the present study we examine the cardiovascular and behavioral responses to nicotine and cytisine administered intrathecally in La Jolla strain (LJ) SHRLJ and age-matched Wistar-Kyoto (WKYLJ) rats. Nicotinic agonists produced augmented pressor, heart rate, and irritation responses in SHRLJ compared with normotensive rats. In both SHRLJ and WKYLJ rats, cytisine elicited a greater nociceptive response and greater spinobulbar component to the pressor response than nicotine. SHRLJ and WKYLJ rats also differ in that the SHRLJ strain shows a diminished tendency for desensitization to cytisine. As in Sprague-Dawley rats, in SHRLJ and WKYLJ rats the cardiovascular and behavioral responses to intrathecal nicotine were significantly inhibited by mecamylamine, dihydro-beta-erthyroidine, and methyllycaconitine. However, methyllycaconitine, which effectively blocked cytisine-elicited cardiovascular and behavioral responses in Sprague-Dawley and WKYLJ rats, was unable to inhibit the maximal rise in cystine-elicited blood pressure, heart rate, and irritation responses in SHRLJ. In contrast to the heightened cardiovascular and behavioral responses, the number of nicotinic binding sites in spinal cord membranes was significantly decreased in the hypertensive rats.(ABSTRACT TRUNCATED AT 250 WORDS)
Department of Pharmacology, University of California, San Diego, La Jolla, CA 92093.
I M
IM
Khan
M P
MP
Printz
T L
TL
Yaksh
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P
Taylor
D000157:Aconitine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000494:pharmacology; D000470:Alkaloids / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D001392:Azocines; D001794:Blood Pressure / Q000187:drug effects*; D004079:Dihydro-beta-Erythroidine / Q000008:administration & dosage / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects*; D006973:Hypertension / Q000503:physiopathology*; D007278:Injections, Spinal; D008297:Male; D008464:Mecamylamine / Q000008:administration & dosage / Q000494:pharmacology; D009043:Motor Activity / Q000187:drug effects; D009538:Nicotine / Q000008:administration & dosage / Q000494:pharmacology*; D018722:Nicotinic Agonists; D011807:Quinolizines; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D013116:Spinal Cord / Q000187:drug effects / Q000502:physiology*; D013239:Stereotyped Behavior / Q000187:drug effects; D000093843:Quinolizidine Alkaloids
D000157:Aconitine; D000470:Alkaloids; D001392:Azocines; D004079:Dihydro-beta-Erythroidine; D008464:Mecamylamine; D009538:Nicotine; D018722:Nicotinic Agonists; D011807:Quinolizines; C054634:methyllycaconitine; C004712:cytisine; D000093843:Quinolizidine Alkaloids