Stimulation of NTS A₁ adenosine receptors evokes counteracting effects on hindlimb vasculature

Abstract

Our previous studies concluded that stimulation of the nucleus of the solitary tract (NTS) A2a receptors evokes preferential hindlimb vasodilation mainly via inducing increases in preganglionic sympathetic nerve activity (pre-ASNA) directed to the adrenal medulla. This increase in pre-ASNA causes the release of epinephrine and subsequent activation of ␤-adrenergic receptors that are preferentially located in the skeletal muscle vasculature. Selective activation of NTS A1 adenosine receptors evokes variable, mostly pressor effects and increases pre-ASNA, as well as lumbar sympathetic activity, which is directed to the hindlimb. These counteracting factors may have opposite effects on the hindlimb vasculature resulting in mixed vascular responses. Therefore, in chloralose-urethane-anesthetized rats, we evaluated the contribution of vasodilator versus vasoconstrictor effects of stimulation of NTS A 1 receptors on the hindlimb vasculature. We compared the changes in iliac vascular conductance evoked by microinjctions into the NTS of the selective A 1 receptor agonist N 6 -cyclopentyladenosine (330 pmol in 50 nl volume) in intact animals with the responses evoked after ␤-adrenergic blockade, bilateral adrenalectomy, bilateral lumbar sympathectomy, and combined adrenalectomy ϩ lumbar sympathectomy. In intact animals, stimulation of NTS A 1 receptors evoked variable effects: increases and decreases in mean arterial pressure and iliac conductance with prevailing pressor and vasoconstrictor effects. Peripheral ␤-adrenergic receptor blockade and bilateral adrenalectomy eliminated the depressor component of the responses, markedly potentiated iliac vasoconstriction, and tended to increase the pressor responses. Lumbar sympathectomy tended to decrease the pressor and vasoconstrictor responses. After bilateral adrenalectomy plus lumbar sympathectomy, a marked vasoconstriction in iliac vascular bed still persisted, suggesting that the vasoconstrictor component of the response to stimulation of NTS A 1 receptors is mediated mostly via circulating factors (e.g., vasopressin, angiotensin II, or circulating catecholamines released from other sympathetic terminals). These data strongly suggest that stimulation of NTS A 1 receptors exerts counteracting effects on the iliac vascular bed: activation of the adrenal medulla and ␤-adrenergic vasodilation versus vasoconstriction mediated by neural and humoral factors.nucleus of the solitary tract; purinergic receptors; ␤-adrenergic blockade; adrenalectomy; lumbar sympathectomy; iliac vascular conductance NUMEROUS STUDIES from our laboratory and by others have shown that adenosine modulates cardiovascular control at the level of the nucleus of the solitary tract (NTS) (3, 4, 11, 12, 17-22, 24, 25). The NTS contains the greatest density of adenosine uptake sites in the central nervous system (5). Therefore, the physiological role of adenosine operating as a neuromodulator in the NTS appears potentially important. A natural source of adenosine in the NTS and other cardiovascular centers is...

Neural and humoral control of regional vascular beds via A1 adenosine receptors located in the nucleus tractus solitarii

“…Selective stimulation of A 1 vs. A 2a receptors often, but not always, exerts counteracting hemodynamic effects. Stimulation of A 1 adenosine receptors in the NTS yields predominately pressor and vasoconstrictor effects in the hindlimb accompanied with differential regional sympathoactivation (adrenal Ͼ renal Ն lumbar) (24,39). In contrast, NTS A 2a adenosine receptor stimulation yields depressor responses, decreases in renal sympathetic nerve activity (RSNA), no changes in lumbar sympathetic nerve activity (LSNA), and activation of preganglionic adrenal sympathetic nerve activity (pre-ASNA) (36,37).…”

Sistemas neuromodulatórios: implicações fisiopatológicas

“…Barraco e Phillis (1991) reportaram que a estimulação dos receptores A1 e A2a no subnúcleo subpostremal do NTS provoca uma resposta pressora e depressora, respectivamente. Também modula a freqüência cardíaca, assim como outras eferências simpáticas (Barraco et al, 1988;McClure et al, 2005;Mosqueda-Garcia et al, 1991;Tseng et al, 1988). Embora a resposta pressora à estimulação dos receptores A1 prevaleça, Scislo e O'Leary (2002) mostraram que em aproximadamente 30% dos casos uma resposta bifásica ou depressora são também observadas.…”

“…Barraco e Phillis (1991) observaram que, a estimulação dos receptores A1 de adenosina no NTS além de provocar uma resposta pressora também aumenta a freqüência cardíaca e a atividade de outras eferências simpáticas (Barraco et al, 1988;McClure et al, 2005;Mosqueda-Garcia et al, 1991;Tseng et al, 1988). Embora a resposta pressora à ativação dos receptores A1 de adenosina prevaleça foram observadas respostas bifásicas ou depressoras em aproximadamente 30% dos casos (Scislo & O'Leary, 2002 É interessante notar que a estimulação dos receptores A1 e A2a no NTS provoca uma resposta simpática regional diferenciada (Scislo et al, 2001).…”

“…Também pode aumentar ou diminuir a freqüência cardíaca e outras eferências simpáticas regionais (Barraco et al, 1988;McClure et al, 2005;MosquedaGarcia et al, 1991;Tseng et al, 1988).…”

“…Barraco e Phillis (1991) mostraram que a estimulação dos receptores A1 de adenosina no subnúcleo subpostremal do NTS provoca uma resposta pressora. Também foi reportado um aumento na freqüência cardíaca e em outras eferências simpáticas regionais (Barraco et al, 1988;McClure et al, 2005;Mosqueda-Garcia et al, 1991;Tseng et al, 1988).…”