Spinal nicotinic receptor activity in a genetic model of hypertension.
Intrathecal cytisine, a nicotinic receptor agonist, elicits greater dose-dependent increases in blood pressure, heart rate and nociceptive responses in SHR than normotensive rat strains. Similar to adult rats, cardiovascular and nociceptive responses were augmented in prehypertensive SHR than age-matched WKY. While hydralazine or captopril pretreatment significantly lowered blood pressure in both SHR and WKY rats, responses to i.t. cytisine were still greater in SHR. By contrast, i.t. cytisine elicited responses were not exaggerated in DOCA-salt hypertensive WKY rats. Pressor and irritation responses to i.t. cytisine can be divided into a transient, initial and persisting, late phases. Both are augmented in SHR. In F1 rats, only the late phase pressor and pain responses to i.t. cytisine are similar in magnitude to those observed in SHR suggesting a possible dominant trait in the SHR. Overall, our findings suggest that hyper-responsiveness in nociception and pressor activity to spinal cytisine in SHR may be pathogenetically associated, but not a consequence, of hypertension.
Khan
I M
IM
Department of Pharmacology, University of California, San Diego 92093-0636, USA. ikhan@ucsd.edu
Stanislaus
S
S
Zhang
L
L
Vaughn
D
D
Printz
M P
MP
Yaksh
T L
TL
Taylor
P
P
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage; D001392:Azocines; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000008:administration & dosage; D003900:Desoxycorticosterone; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006830:Hydralazine / Q000008:administration & dosage; D006973:Hypertension / Q000139:chemically induced / Q000188:drug therapy* / Q000235:genetics; D008297:Male; D023421:Models, Animal; D010147:Pain Measurement; D011807:Quinolizines; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011978:Receptors, Nicotinic / Q000187:drug effects* / Q000378:metabolism; D013045:Species Specificity; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism; D000093843:Quinolizidine Alkaloids
D000470:Alkaloids; D000959:Antihypertensive Agents; D001392:Azocines; D002216:Captopril; D003900:Desoxycorticosterone; D006830:Hydralazine; D011807:Quinolizines; D011978:Receptors, Nicotinic; C004712:cytisine; D000093843:Quinolizidine Alkaloids