Modulation of inducible nitric oxide synthase (iNOS) expression and cardiovascular responses during static exercise following iNOS antagonism within the ventrolateral medulla

Abstract

Previous reports indicate that inducible nitric oxide synthase (iNOS) blockade within the rostral ventrolateral medulla (RVLM) and caudal ventrolateral medulla (CVLM) differentially modulated cardiovascular responses, medullary glutamate, and GABA concentrations during static skeletal muscle contraction. In the current study, we determined the role of iNOS antagonism within the RVLM and CVLM on cardiovascular responses and iNOS protein expression during the exercise pressor reflex in anesthetized rats. Following 120 min of bilateral microdialysis of a selective iNOS antagonist, aminoguanidine (AGN; 10 µM), into the RVLM, the pressor responses were attenuated by 72 % and changes in heart rate were reduced by 38 % during a static muscle contraction. Furthermore, western blot analysis of iNOS protein abundance within the RVLM revealed a significant attenuation when compared to control animals. In contrast, bilateral administration of AGN (10 µM) into the CVLM augmented the increases in mean arterial pressure by 60 % and potentiated changes in heart rate by 61 % during muscle contractions, but did not alter expression of the iNOS protein within the CVLM. These results demonstrate that iNOS protein expression within the ventrolateral medulla is differentially regulated by iNOS blockade that may, in part, contribute to the modulation of cardiovascular responses during static exercise.

Endothelial Nitric Oxide Synthase (eNOS) and the Cardiovascular System: in Physiology and in Disease States

“…A plethora of molecular mechanisms, neurotransmitters, receptors, and reciprocal pathways are involved within these two RVLM and CVLM areas as well as other higher regions of the brain that are collectively known as the "central command". Pharmacological manipulations by L-arginine, the NO precursor, or by nNOS, iNOS, and eNOS antagonists are involved in the modulation of the Exercise Pressor Reflex [1,180]. A brief schematic diagram of the Exercise Pressor Reflex is shown in (Figure 4).…”

Energy restriction, exercise and atorvastatin treatment improve endothelial dysfunction and inhibit miRNA-155 in the erectile tissue of the aged rat.

“…The asymptomatic antecedent of these entities that insidiously develop along time, is endothelial dysfunction (ED) [ 2 ], which is characterized by a decrease in bioavailability of nitric oxide (NO). NO is a gaseous molecule, constitutively produced by endothelial NO synthase (eNOS) in endothelial cells, that diffuses into the smooth muscle cell (SMC) layer and induces its relaxation [ 3 ]. Under pro-inflammatory conditions, inducible NOS (iNOS) is activated, forming high levels of NO and exhausting the substrate and co-factor shared with eNOS.…”