Differential cardiovascular responses to blockade of nNOS or iNOS in rostral ventrolateral medulla of the rat

1 We investigated the contribution of neuronal or inducible nitric oxide sy nthase (nNOS or iNOS) at the rostral ventrolateral medulla (RVLM) to centra l cardiovascular regulation by endogenous nitric oxide (NO), using Sprague- Dawley rats anaesthetized and maintained with propofol. 2 Microinjection bilaterally into the RVLM of a NO trapping agent, carboxy- 2-phenyl-4,4,5,5-tetramethylimidazoline-1-oxy-1-3-oxide (10, 50 or 100 nmol es) resulted in significant hypotension and bradycardia. 3 Similar application of a selective antagonist of nNOS, 7-nitroindazole (1 , 2.5 or 5 pmoles), or selective antagonists of iNOS, aminoguanidine (125, 250 or 500 pmoles), N-6-(1-iminoethyl)-L-lysine (250 pmoles) or S-methyliso thiourea (250 pmoles), induced respectively a reduction or on enhancement i n systemic arterial pressure, heart rate and power density of the vasomotor components in the spectrum of arterial blood pressure signals, the experim ental index for sympathetic neurogenic vasomotor tone. 4 Both hypotension and bradycardia induced by the NO precursor, L-arginine (100 nmoles), were significantly blunted when aminoguanidine (250 pmoles) w as co-microinjected bilaterally into the RVLM. On the other hand, co-admini stered 7-nitroindazole (2.5 pmoles) was ineffective. 5 Whereas low doses of S-nitro-N-acetylpenicillamine (0.25 or 0.5 nmoles) e licited hypertension and tachycardia, high doses of this non-nitrate NO don or (5 nmoles) induced hypotension and bradycardia. 6 Reverse transcription-polymerase chain reaction analysis revealed that bo th iNOS and nNOS mRNA were expressed in the ventrolateral medulla. 7 We conclude that the prevalence of nNOS over iNOS activity at the RVLM an d the associated dominance of sympathoexcitation over sympathoinhibition ma y underlie the maintenance of sympathetic vasomotor outflow and stable syst emic arterial pressure by the endogenous NO.