Vasopressin is a major vasoconstrictor involved in hindlimb vascular responses to stimulation of adenosine A₁ receptors in the nucleus of the solitary tract

Abstract

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.

Interaction of medullary P2 and glutamate receptors mediates the vasodilation in the hindlimb of rat

“…For instance, in cat, stimulation of the HDA elicits monosynaptic excitatory [11] and inhibitory [10] postsynaptic potentials in NTS neurons that receive inputs from baroreceptors. Thirdly, HDA stimulation elicits rapid adenosine release in the NTS derived from extracellular ATP [20], presumably eliciting a β-adrenergic iliac vasodilation that is overridden by a vasopressinergic vasoconstriction [41,42]. Nonetheless, subunits of P2 receptors are expressed in NTS neurons of rat [14,15]; and the reductions in HVC responses seen here can be explained by blockade of input signals from the HDA to the NTS [7,8], independent of the pathways in control of AP and HR increases.…”

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

“…The relative contribution of three neural and humoral vasoactive factors (sympathetic and vasopressinergic vasoconstriction opposed by ␤-adrenergic vasodilation) to the regional vascular responses evoked by selective stimulation of NTS A 1 adenosine receptors was studied in 53 male Sprague-Dawley rats. Our previous studies showed that only these three vasoactive factors significantly contributed to iliac vascular responses evoked by stimulation of NTS A 1 adenosine receptors (25). The relative changes in iliac (IVC), mesenteric (MVC), and renal (RVC) vascular conductance evoked by microinjections into the NTS by the selective A 1 adenosine receptor agonist CPA (Tocris) observed in intact animals (n ϭ 8) were compared with the responses evoked after the following six experimental procedures: protocol 1, bilateral adrenalectomy (ADX, n ϭ 8); protocol 2, blockade of ␤-adrenergic receptors (n ϭ 7); protocol 3, selective vasopressin V1 receptor blockade (VX, n ϭ 7); protocol 4, sinoaortic denervation (SAD, n ϭ 7); protocol 5, bilateral adrenalectomy combined with selective vasopressin V1 receptor blockade (ADX ϩ VX, n ϭ 8); and protocol 6, sinoaortic denervation combined with bilateral adrenalectomy (SAD ϩ ADX, n ϭ 8).…”

“…All procedures were described in detail previously (2,21,24,25,32,(37)(38)(39). Briefly, male SpragueDawley rats (350 -400 g; Charles River) were anesthetized with a mixture of ␣-chloralose (80 mg/kg) and urethane (500 mg/kg) intraperitoneally, tracheotomized, connected to a small animal respirator (SAR-830; CWE, Ardmore, PA), and artificially ventilated with a 40% oxygen-60% nitrogen mixture.…”

“…Vasopressin V1 receptors, mediating vascular constriction, were blocked by intravenous injections of [␤-mercapto-␤,␤-cyclopentylmethylenepropionyl, 1 -O-Me-Tyr, 2 Arg 8 ]-vasopressin, a selective V1 antagonist (20 g/kg; Sigma) in doses that completely blocked vasoconstriction evoked by intavenous injection of vasopressin (50 mU/kg; Sigma). The blockades were applied ϳ10 min before the microinjection in the NTS (24,25). Sinoaortic denervation was accomplished at the beginning of surgery, as described previously (33,39).…”

“…However, stimulation of A 1 adenosine receptors alone in the NTS often yields variable responses, although predominantly pressor and iliac vasoconstrictor responses prevail (24,39). Recent studies have attributed this variability to the activation of the adrenal medulla, the subsequent release of epinephrine eliciting activation of ␤-adrenergic vasodilation that is simultaneously opposed by sympathetic and vasopressinergic vasoconstriction (24,25). The increased vasoconstrictor drive and simultaneously triggered ␤-adrenergic vasodilation were most likely mediated via inhibition of NTS baroreflex mechanisms (32,34,39).…”