Cardiovascular effects of 5HT2 and 5HT3 receptor stimulation in the nucleus tractus solitarius of spontaneously hypertensive rats.
The effects of local application of 5-HT2- and 5-HT3-receptor agonists in the nucleus tractus solitarius (NTS) on the cardiovascular parameters were investigated in anaesthetized spontaneously hypertensive (SH) rats and their genetically normotensive precursors (WKY). Unilateral microinjection of picomolar doses of a 5HT2 receptor agonist, 2,5-dimethoxy-3-bromo-amphetamine (DOB, 0.025-0.5 pmol), produced a dose-dependent hypotension and bradycardia in both SH and WKY rats. These effects could be prevented by prior local microinjection of a 5-HT2 receptor antagonist, ketanserin (10 pmol). However, for both cardiovascular parameters, DOB was more potent in SH than in WKY rats. Thus, the dose-related responses to DOB were shifted to the left in SH as compared to WKY rats. Bilateral microinjection of the 5-HT3 receptor agonist, phenylbiguanide (1.7-5 nmol), produced an increase in blood pressure and reduced the cardiovagal component of the baroreflex. These effects were not significantly different in SH and WKY rats. These data suggest that 5-HT2 receptors, but not 5-HT3 receptors, are supersensitive in the NTS of SH rats.
Merahi
N
N
INSERM U288, CHU Pitié-Salpêtrière, Paris, France.
Laguzzi
R
R
D000661:Amphetamine / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D011985:Receptors, Serotonin / Q000187:drug effects* / Q000502:physiology; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D017552:Solitary Nucleus / Q000187:drug effects* / Q000502:physiology
D011985:Receptors, Serotonin; D017366:Serotonin Receptor Agonists; D000661:Amphetamine