Role of the arterial baroreflex in 5-HT1A receptor agonist-mediated sympathoexcitation following hypotensive hemorrhage.
5-HT1A-receptor agonists rapidly restore blood pressure and sympathetic activity in conscious rats subjected to hypotensive hemorrhage. 5-HT1A-receptor activation has also been shown to produce a robust increase in baroreceptor-dependent, pulse-synchronous firing of cardiac sympathetic nerves in anesthetized cats. To determine whether 5-HT1A-receptor agonists reverse hemorrhage-induced suppression of sympathetic activity through facilitation of the arterial baroreflex, the effects of the 5-HT1A-receptor agonist, 8-OH-DPAT, were assessed in male Sprague-Dawley rats subjected to sinoaortic baroreceptor denervation and subsequent hypotensive hemorrhage. 8-OH-DPAT produced rapid pressor and sympathoexcitatory responses in hemorrhaged animals that were attenuated, but not blocked, by sinoaortic denervation (SAD) (+49 +/- 4 vs. +37 +/- 4 mmHg; +165 +/- 30 vs. +92 +/- 24% baseline, P < 0.01). Spectral analysis of sympathetic activity showed that SAD abolished the 8-hydroxy-2-(di-n-propylamino)-tetralin (8-OH-DPAT)-mediated increases in pulse-synchronous (13 +/- 1 vs. 5 +/- 1% total power for intact vs. SAD rats, P < 0.01) and Mayer wave-related bursting (18 +/- 3 vs. 8 +/- 1% total power, P < 0.05). However, 8-OH-DPAT continued to increase total power (+72 +/- 22 vs. -63 +/- 7% prehemorrhage total power, P < 0.05) and power at the respiratory frequency (35 +/- 2 vs. 25 +/- 4% total power) in SAD animals. These data indicate that full expression of the sympathoexcitatory effect of 8-OH-DPAT requires a functional arterial baroreflex. However, a portion of the effect is due to activation of arterial baroreflex-independent sympathetic pathways.
Osei-Owusu
Patrick
P
Dept. of Pharmacology and Experimental Therapeutics, Loyola Univ. Chicago, Stritch School of Medicine, 2160 First Ave., Maywood, IL 60153, USA.
Scrogin
Karie
K
D017371:8-Hydroxy-2-(di-n-propylamino)tetralin / Q000494:pharmacology; D000818:Animals; D017704:Baroreflex / Q000502:physiology*; D003627:Data Interpretation, Statistical; D003714:Denervation; D004567:Electrodes, Implanted; D006470:Hemorrhage / Q000150:complications / Q000503:physiopathology*; D007022:Hypotension / Q000209:etiology / Q000503:physiopathology*; D020896:Hypovolemia / Q000503:physiopathology; D008297:Male; D051381:Rats; D017207:Rats, Sprague-Dawley; D044282:Receptor, Serotonin, 5-HT1A / Q000502:physiology*; D017366:Serotonin Receptor Agonists / Q000494:pharmacology*; D012849:Sinoatrial Node / Q000503:physiopathology; D013564:Sympathetic Nervous System / Q000503:physiopathology*
D017366:Serotonin Receptor Agonists; D044282:Receptor, Serotonin, 5-HT1A; D017371:8-Hydroxy-2-(di-n-propylamino)tetralin