title: Selective sensitization by nitric oxide of sympathetic baroreflex in rostral ventrolateral medulla of conscious rabbits.
abstract: Nitric oxide (NO) deficiency in the rostral ventrolateral medulla (RVLM) has been implicated in impaired baroreflex control in hypertensive and heart failure animals. However, the role of local NO in normal baroreflex regulation remains unclear. This study aimed to examine the role of NO in tonic and baroreflex control of blood pressure (BP) in the RVLM of conscious rabbits. Microinjections of NO donors, S-nitroso-N-acetylpenicillamine and sodium nitroprusside (5 to 20 nmol), or NO itself (20 to 200 pmol) into the RVLM dose-dependently increased BP. Bilateral microinjections of an NO synthase (NOS) inhibitor NG-nitro-L-arginine methyl ester (L-NAME; 10 nmol), its inactive enantiomer D-NAME, or soluble guanylate cyclase (sGC) inhibitors, 1-H-[1,2,4]oxadiaolo[4,3-a]quinoxalin-1-one (ODQ, 250 pmol) and methylene blue (10 nmol), into the RVLM did not affect resting BP, heart rate, or renal sympathetic nerve activity (RSNA). However, L-NAME, methylene blue, and ODQ decreased RSNA baroreflex gain by 42% to 55%, whereas D-NAME did not affect this reflex. Co-microinjections of L-NAME and superoxide scavenger tempol (20 nmol) decreased RSNA baroreflex gain by 37+/-8%. Microinjections of a neuronal NOS (nNOS) inhibitor, 7-nitroindazole (500 pmol), into the RVLM decreased RSNA baroreflex gain by 42+/-12%, without altering resting BP, heart rate, or RSNA. Local administration of inducible NOS (iNOS) inhibitors, S-methylisothiourea (0.25 nmol) and aminoguanidine (0.25 and 2.5 nmol), affected neither resting nor baroreflex parameters. These results suggest that nNOS-derived NO facilitates sympathetic baroreflex transmission in the RVLM at least in part via a sGC-dependent, superoxide-independent mechanism. However, local nNOS and iNOS play little role in the tonic support of BP in conscious rabbits.
authors.affiliation: Baker Heart Research Institute, Melbourne, Victoria, Australia. dmitry.mayorov@baker.edu.au
authors.forename: Dmitry N
authors.initials: DN
authors.lastname: Mayorov
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000008:administration & dosage / Q000494:pharmacology; D017704:Baroreflex / Q000187:drug effects* / Q000502:physiology; D003497:Cyclic N-Oxides / Q000008:administration & dosage / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000494:pharmacology; D006162:Guanylate Cyclase / Q000037:antagonists & inhibitors / Q000737:chemistry; D008526:Medulla Oblongata / Q000187:drug effects*; D008845:Microinjections; D019331:NG-Nitroarginine Methyl Ester / Q000008:administration & dosage / Q000494:pharmacology; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors; D009569:Nitric Oxide / Q000008:administration & dosage / Q000494:pharmacology*; D020030:Nitric Oxide Donors / Q000008:administration & dosage / Q000494:pharmacology*; D019001:Nitric Oxide Synthase / Q000037:antagonists & inhibitors; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D011817:Rabbits; D012995:Solubility; D013113:Spin Labels; D013564:Sympathetic Nervous System / Q000187:drug effects*
chemical_list: D000975:Antioxidants; D003497:Cyclic N-Oxides; D004791:Enzyme Inhibitors; D009419:Nerve Tissue Proteins; D020030:Nitric Oxide Donors; D013113:Spin Labels; D009569:Nitric Oxide; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D006162:Guanylate Cyclase; C001803:tempol; D019331:NG-Nitroarginine Methyl Ester