Effects of nicotine on brain stem mechanisms of cardiovascular control.
The role of the central nervous system in the pressor effect of nicotine is not well understood. In this study, we evaluated the cardiovascular effects of nicotine in the lower brainstem of normotensive and hypertensive rats. Microinjection of nicotine (0.012-3696 pmol/60 nl) into the nucleus of the solitary tract and area postrema of Sprague-Dawley (SD), Wistar Kyoto (WKY) and spontaneously hypertensive rats (SHR) decreased blood pressure and heart rate. In contrast, administration of similar doses of nicotine within the rostral ventrolateral medulla (RVLM) evoked a long-lasting pressor and tachycardic effect. This pressor effect was completely abolished by prior microinjection of hexamethonium. In SHR the depressor and bradycardic responses in the nucleus of the solitary tract and area postrema were similar to those of normotensive animals. The pressor effect in the RVLM, however, was more pronounced in the SHR than in WKY or SD rats. In additional experiments, the changes produced by intra-RVLM administration of nicotine on renal sympathetic nerve activity, blood pressure and heart rate were evaluated before and after equidepressor intravenous doses of either clonidine, labetalol or prazosin. The prior administration of labetalol antagonized the pressor effect of nicotine in the three strains of rats (SHR, 82 +/- 6%; SD, 96 +/- 4%; WKY, 83 +/- 9%). Prazosin inhibited the nicotine pressor response by 69% in SHR, by 44% in SD and by 70% in WKY. Clonidine had no effect on nicotine response in the three groups of rats. In conclusion, nicotine administration within the RVLM increases renal sympathetic nerve activity and blood pressure.(ABSTRACT TRUNCATED AT 250 WORDS)
Tseng
C J
CJ
Division of Clinical Pharmacology, Vanderbilt University, Nashville, Tennessee.
Appalsamy
M
M
Robertson
D
D
Mosqueda-Garcia
R
R
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D001933:Brain Stem / Q000187:drug effects* / Q000502:physiology; D002320:Cardiovascular Physiological Phenomena; D002319:Cardiovascular System / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D018738:Hexamethonium; D006584:Hexamethonium Compounds / Q000494:pharmacology; D007741:Labetalol / Q000494:pharmacology; D008297:Male; D009538:Nicotine / Q000494:pharmacology*; D010830:Physostigmine / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D017207:Rats, Sprague-Dawley
D000959:Antihypertensive Agents; D006584:Hexamethonium Compounds; D018738:Hexamethonium; D009538:Nicotine; D010830:Physostigmine; D003000:Clonidine; D007741:Labetalol; D011224:Prazosin