DMPP-evoked increases in postganglionic sympathetic nerve activity and blood pressure occurs by two mechanisms in the rat.
1. Intravenous administration of the ganglionic nicotinic receptor agonist DMPP (1,1-dimethyl-4-phenylpiperazinium iodide) into urethane-anaesthetized rats evoked dose-dependent increases in mean arterial pressure (MAP) and renal sympathetic nerve activity (RSNA). 2. The ganglionic nicotinic receptor antagonists pentolinium and hexamethonium either alone or combined did not inhibit the increase in RSNA and MAP evoked by 50 to 200 micrograms kg-1 doses of DMPP. The increase in renal sympathetic nerve activity evoked by DMPP occurred as a brief burst in firing. 3. The increase in MAP, but not RSNA, evoked by DMPP in the presence of pentolinium was inhibited by the selective alpha 1-adrenergic receptor antagonist prazosin. 4. The non-selective alpha-adrenoceptor and NPY receptor antagonist benextramine also inhibited the increase in MAP without inhibiting the increase in RSNA. Surprisingly, the combination of benextramine and pentolinium, or benextramine and hexamethonium, completely blocked the DMPP-evoked increase in RSNA and thus the increase in MAP. 5. The uptake1 antagonist desipramine combined with pentolinium did not affect the DMPP-evoked increases in MAP or RSNA when compared to the responses evoked in the presence of pentolinium alone. 6. Adding the selective M1 muscarinic receptor antagonist telenzepine to pentolinium and prazosin did not inhibit the increase in RSNA evoked by a 100 micrograms kg-1 dose of DMPP. 7. While the DMPP-evoked increase in MAP in the presence of ganglionic nicotinic receptor antagonists is primarily dependent upon activation of alpha 1-adrenoceptors, the increase in RSNA occurs via activation of ganglionic nicotinic receptors and activation of a mechanism susceptible to blockade by benextramine.
Martin
J R
JR
Department of Pharmacology, Kirksville College of Osteopathic Medicine, MO 63501, USA.
D018759:Adrenergic Uptake Inhibitors / Q000494:pharmacology; D000317:Adrenergic alpha-Antagonists / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects*; D003891:Desipramine / Q000494:pharmacology; D004246:Dimethylphenylpiperazinium Iodide / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D005731:Ganglionic Stimulants / Q000494:pharmacology*; D008297:Male; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010425:Pentolinium Tartrate / Q000494:pharmacology; D011224:Prazosin / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017779:Sympathetic Fibers, Postganglionic / Q000187:drug effects*
D018759:Adrenergic Uptake Inhibitors; D000317:Adrenergic alpha-Antagonists; D005731:Ganglionic Stimulants; D018733:Nicotinic Antagonists; D004246:Dimethylphenylpiperazinium Iodide; D010425:Pentolinium Tartrate; D003891:Desipramine; D011224:Prazosin