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...
Our previous study showed that stimulation of adenosine A1 receptors located in the nucleus of the solitary tract (NTS) exerts counteracting effects on the iliac vascular bed: activation of the adrenal medulla and -adrenergic vasodilation versus vasoconstriction mediated by neural and unknown humoral factors. In the present study we investigated the relative contribution of three major potential humoral vasoconstrictors: vasopressin, angiotensin II, and norepinephrine in this response. In urethane-chloralose anesthetized rats we compared the integral changes in iliac vascular conductance evoked by microinjections into the NTS of the selective A1 receptor agonist N 6 -cyclopentyladenosine (CPA; 330 pmol in 50 nl) in intact (Int) animals and following: V1 vasopressin receptor blockade (VX), angiotensin II AT1 receptor blockade (ATX), bilateral adrenalectomy ϩ ganglionic blockade (ADX ϩ GX; which eliminated the potential increases in circulating norepinephrine and epinephrine), ADX ϩ GX ϩ VX and ADX ϩ GX ϩ VX ϩ ATX. In Int animals, stimulation of NTS A1 adenosine receptors evoked typical variable responses with prevailing pressor and vasoconstrictor effects. VX reversed the responses to depressor ones. ATX did not significantly alter the responses. ADX ϩ GX accentuated pressor and vasoconstrictor responses, whereas ADX ϩ GX ϩ VX and ADX ϩ GX ϩ VX ϩ ATX virtually abolished the responses. Stimulation of NTS A1 adenosine receptors increased circulating vasopressin over fourfold (26.4 Ϯ 10.4 vs. 117.0 Ϯ 19 pg/ml). These data strongly suggest that vasopressin is a major vasoconstrictor factor opposing -adrenergic vasodilation in iliac vascular responses triggered by stimulation of NTS A1 adenosine receptors, whereas angiotensin II and norepinephrine do not contribute significantly to the vasoconstrictor responses.
Our previous studies showed that stimulation of adenosine A 1 receptors located in the nucleus of the solitary tract (NTS) exerts counteracting effects on the iliac vascular bed: activation of the adrenal medulla and -adrenergic vasodilation vs. sympathetic and vasopressinergic vasoconstriction. Because NTS A 1 adenosine receptors inhibit baroreflex transmission in the NTS and contribute to the pressor component of the HDR, we hypothesized that these receptors also contribute to the redistribution of blood from the visceral to the muscle vasculature via prevailing sympathetic and vasopressinergic vasoconstriction in the visceral (renal and mesenteric) vascular beds and prevailing -adrenergic vasodilation in the somatic (iliac) vasculature. To test this hypothesis, we compared the A 1 adenosine-receptor-mediated effects of each vasoactive factor triggered by NTS A 1 adenosine receptor stimulation [N 6 -cyclopentyladenosine (CPA), 330 pmol in 50 nl] on the regional vascular responses in urethane/chloralose-anesthetized rats. The single-factor effects were separated using adrenalectomy, -adrenergic blockade, V 1 vasopressin receptor blockade, and sinoaortic denervation. In intact animals, initial vasodilation was followed by large, sustained vasoconstriction with smaller responses observed in renal vs. mesenteric and iliac vascular beds. The initial -adrenergic vasodilation prevailed in the iliac vs. mesenteric and renal vasculature. The large and sustained vasopressinergic vasoconstriction was similar in all vascular beds. Small sympathetic vasoconstriction was observed only in the iliac vasculature in this setting. We conclude that, although A 1 adenosine-receptor-mediated -adrenergic vasodilation may contribute to the redistribution of blood from the visceral to the muscle vasculature, this effect is overridden by sympathetic and vasopressinergic vasoconstriction. purinergic receptors; V 1 receptor blockade; -adrenergic blockade; adrenalectomy; sinoaortic denervation; iliac vascular conductance; mesenteric vascular conductance; renal vascular conductance RECENT STUDIES HAVE FIRMLY established that adenosine operating as a neuromodulator in the nucleus of the solitary tract (NTS) modifies cardiovascular control (14, 20, 24, 25, 34, 40 -44). The NTS is a major integrative center for visceral and autonomic reflexes and contains the greatest density of adenosine uptake sites within the central nervous system (4). Adenosine operates in the NTS in both physiological and pathological situations. Under normal, physiological conditions, a natural source of adenosine is ATP released from neurons and glial cells (6). This occurs, for example, during the stress or hypothalamic defense response (HDR) (42-44). Extracellular ATP is catabolized via ectonucleotidases to adeno-
Our previous studies showed that stimulation of NTS adenosine A1 receptors exerts variable, counteracting effects on the iliac vascular bed: activation of the adrenal medulla and β‐adrenergic vasodilation vs. vasoconstriction mediated by sympathetic nerves and vasopressin (McClure et al. Am J Physiol Heart Circ Physiol 289: –H2542; 2005 ; FASEB 20: , 2006). Vasopressin and β‐adrenergic receptors are differentially expressed in various vascular beds. Therefore we investigated the role of these humoral factors in NTS A1 receptor mediated regional vascular responses. We compared the responses of iliac vs. mesenteric and renal vascular conductance (IVC, MVC and RVC, respectively) in 4 groups of chloralose/urethane anesthetized rats: intact (INT), following β‐adrenergic blockade (βX), bilateral adrenalectomy (ADX) and vasopressin V1 receptor blockade (VX). In INT, typical biphasic responses were observed: early vasodilation (tended: IVC=RVC>MVC) followed by vasoconstriction. Both ADX and βX abolished the vasodilation (to a greater extent in βX). VX abolished/reversed iliac and mesenteric but not renal vasoconstrictor responses. We conclude that β‐adrenergic and vasopressinergic mechanisms differentially contribute to regional vascular responses evoked by stimulation of NTS adenosine A1 receptors. NIH HL‐67814
Our previous study showed that stimulation of NTS A1 adenosine receptors exerts counteracting effects on the iliac vascular bed: activation of the adrenal medulla and β‐adrenergic vasodilation vs. vasoconstriction mediated by neural and unknown humoral factors (Am J Physiol 289:H2536‐H2542, 2005). The follow up study identified vasopressin as a potential humoral factor involved: systemic blockade of V1 vasopressin receptors abolished/reversed iliac vasoconstriction (FASEB 20: A363, 2006). Stimulation of NTS A1 adenosine receptors attenuates the baroreflex (FASEB 21: A466, 2007), thus may increase circulating vasopressin. Therefore in the present study we compared circulating vasopressin levels before and after microinjections into the NTS of selective A1 adenosine receptor agonist N6cyclopentyladenosine (CPA, 330 pmol/50nl) or vehicle (artificial cerebrospinal fluid, ACF, 50 nl), using the same experimental model as previously (chloralose/urethane anesthetized rats). CPA increased circulating vasopressin over 4‐fold (117.0±19.0 vs. 26.4±10.4 pg/ml, P=0.0006, n=8) whereas ACF did not increase vasopressin level significantly (50.9±11.3 vs. 25.0±7.2 pg/ml, P=0.083, n=5). We conclude that stimulation of NTS A1 adenosine receptors increases circulating vasopressin probably via inhibition of NTS baroreflex mechanisms. NIH HL‐67814
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