Cotransmission from sympathetic vasoconstrictor neurons: differences in guinea-pig mesenteric artery and vein
Introduction
There is growing appreciation that peripheral nerves release more than one transmitter, a process referred to as plurichemical neurotransmission or cotransmission (Furness et al., 1989, Burnstock, 1990). The evidence for cotransmission is particularly strong for postganglionic sympathetic nerves, which have been shown to corelease adenosine 5′-triphosphate (ATP), neuropeptide Y (NPY) and noradrenaline (NA) (for reviews, see Stjärne, 1989, Burnstock, 1990, Westfall et al., 1991, Lundberg, 1996). However, the relative contribution of each of these neurotransmitters to contraction varies significantly between blood vessels. For example, both NA and ATP significantly contribute to sympathetic neural responses in rabbit saphenous and jejunal artery, and in guinea-pig submucosal arterioles (see Burnstock, 1995). In contrast, it is more difficult to reveal a nonadrenergic component of nerve stimulation in rat tail artery (see Burnstock, 1995), even though ATP is released during nerve stimulation in this vessel (Msghina et al., 1992, Mutafova-Yambolieva and Westfall, 1998).
Both arteries and veins contain smooth muscle and both are innervated by sympathetic nerves. However, the physiological roles of high-pressure arteries versus low-pressure veins differ significantly from one another, i.e., in the splanchnic circulation, arteries and arterioles contribute to total peripheral resistance and control the local flow of blood to the gastrointestinal tract. In contrast, the venous side of the splanchnic circulation has a storage capacity and, hence, contributes to the regulation of blood volume and venous return, a role referred to as capacitance. Thus, sympathetic nerves have been shown to play significantly different roles in controlling the arterial and venous sides of the splanchnic circulation (see Hansen et al., 1998).
The goal of the present study was to investigate cotransmission in the splanchnic circulation by comparing vessels taken from the two functionally distinct portions of this vascular bed, i.e., mesenteric arteries and veins.
The electrical and contractile response elicited with stimulation of sympathetic nerves has been shown to differ significantly between arteries and veins. In arteries (including the guinea-pig mesenteric artery), sympathetic nerve stimulation gives rise to rapidly rising excitatory junction potentials (EJPs) of brief duration that are resistant to prazosin, but are blocked by α,β-methylene ATP (α,βMeATP) (see Brock and Cunnane, 1992, Kreulen, 1986, Hottenstein and Kreulen, 1987). ATP is considered to be a prime candidate to mediate these EJPs (Burnstock, 1990, Stjärne et al., 1994). In contrast to arteries, fast EJPs are generally not observed with sympathetic nerve stimulation in veins (including the guinea-pig mesenteric vein). Rather, repetitive nerve stimulation in vein typically produces a slow depolarization (Suzuki, 1981) that is resistant to purinoceptor desensitization with α,βMeATP (Hottenstein and Kreulen, 1987, Hirst and Jobling, 1989). This has led to the conclusion that ATP is not involved in these junctional events (Hottenstein and Kreulen, 1987, Hirst and Jobling, 1989) and, hence, is not released during nerve stimulation. However, in a study measuring ATP release in vein (i.e., human saphenous vein), the conflicting observation was made that ATP was released together with NA but did not appear to generate the non-adrenergic component of contraction (Rump and von Kügelgen, 1994). Therefore, differences in the mechanical and electrical responses to nerve stimulation between arteries and veins might be accounted for by differences in the end (i.e. postjunctional) effects of released neurotransmitters.
NPY is considered to be a cotransmitter, together with NA and ATP, in the sympathetic nervous system (Lundberg et al., 1990). This peptide is assumed to predominantly mediate responses to higher frequencies of stimulation and therefore play a role specifically at high levels of sympathetic nerve activity (see Lundberg, 1996). NPY is known to cause contraction of the vascular smooth muscles in some regions, such as rat mesenteric arterial bed, human coronary artery, cerebral circulation (Abounader et al., 1995, Macho et al., 1987, Westfall et al., 1987). In some systems, NPY can also play a role as neuromodulator, by potentiating the vasoconstriction produced by other agonists, or by sympathetic nerve stimulation (Cortes et al., 1999) or inhibiting the release of NA (Westfall et al., 1987). The role of this peptide in the mesenteric artery and vein of guinea-pig is unclear.
In the present study, the relative contribution of NA, ATP and NPY to neurally induced contractions in guinea-pig mesenteric artery and vein was established. Autonomic neurotransmission was further characterized morphologically by comparing immunohistochemically the localization of tyrosine-hydroxylase-like immunoreactivity (TH-LI) and NPY-like immunoreactivity (NPY-LI) in artery and vein.
Section snippets
General
Male guinea-pigs (weighing 400 to 450 g) were sacrificed by CO2 overdose followed by exsanguination, in keeping with protocols approved by the University of Nevada’s Animal Care and Use Committee. The aorta, inferior mesenteric artery, vein and associated mesentery were immediately removed from the animal and placed in cold (10°C) oxygenated Krebs solution for further dissection of the mesenteric blood vessels. Segments of first- and second-order branches of the inferior mesenteric artery
Results
The contractile responses to electrical field stimulation (EFS, 0.2–32 Hz) were measured in artery and vein and compared to the response obtained with 70 mM KCl. KCl produced a significantly greater contraction in artery than vein (i.e., 110.25±13.5 mN/mm2 in artery versus 71.4±5.9 mN/min.mm2 in vein, P<0.05). These responses to 70 mM KCl are submaximal in both the artery and vein, i.e., they represent approximately 70% of the maximum contraction developed in response to combined application of
Discussion
Guinea-pig mesenteric artery and vein exhibit significant differences with regard to their electrical and mechanical responses to nerve stimulation (Kreulen, 1986, Hottenstein and Kreulen, 1987, Hirst and Jobling, 1989, Browning et al., 1999). The present study generally confirms these earlier observations and also reveals substantial differences in the role of sympathetic co-transmission in these two vascular networks. Our results suggest that NA is the primary excitatory neurotransmitter in
Acknowledgements
This work was supported by US Public Health Service Grant HL 60031 to V.M-Y.
References (39)
- et al.
Neurochemical classification of myenteric neurons in the guinea-pig ileum
J. Neurosci.
(1996) - et al.
Multiple P2Y receptors mediate contraction in guinea-pig mesenteric vein. The vascular system
Gen. Pharmacol.
(2000) - et al.
Opoid-like immunoreactive neurons in secretomotor pathways of the guinea-pig ileum
Neuroscience
(1990) - et al.
Characterization of neuropeptide Y receptors in human cerebral arteries with selective agonists and the new Y1 antagonist BIBP 3226
Br. J. Pharmacol.
(1995) - Brock, J.A., Cunnane, T.C., 1992. Electrophysiology of neuroeffector transmission in smooth muscle. In: Burnstock, G.,...
- et al.
Two populations of sympathetic neurons project selectively to mesenteric artery or vein
Am. J. Physiol.
(1999) Co-transmission. The Fifth Heymens Memorial Lecture
Arch. Int. Pharmacodyn. Ther.
(1990)Noradrenaline and ATP. Cotransmission and neuromodulators
J. Physiol. Pharmacol.
(1995)- et al.
Synergism between neuropeptide Y and norepinephrine highlights sympathetic cotransmission: studies in rat arterial mesenteric bed with neuropeptide Y, analogs, and BIBP 3226
J. Pharmacol. Exp. Ther.
(1999) - et al.
High force development and crossbridge attachment in smooth muscle from swine carotid arteries
Circ. Res.
(1982)
Chemical coding of neurons and plurichemical transmission
Annu. Rev. Pharmacol. Toxicol.
Endogenous nitric oxide modulates sympathetic neuroeffector transmission in the isolated rabbit lateral saphenous vein
J. Cardiovasc. Pharmacol.
Profile of neurohumoral agents on mesenteric and intestinal blood flow in health and disease
Physiol. Res.
Length–tension relationship of smooth muscle of the hog carotid artery
Circ. Res.
The distribution of γ-adrenoceptors and P2 purinoceptors in mesenteric arteries and veins of the guinea-pig
Br. J. Pharmacol.
Comparison of the frequency dependence of venous and arterial responses to sympathetic nerve stimulation in guinea-pigs
J. Physiol. (Lond.)
Norepinephrine and potassium induced calcium translocation in rat vas deferens
J. Pharmacol. Exp. Ther.
Activation of mesenteric arteries and veins by preganglionic and postganglionic nerves
Am. J. Physiol.
Neuropeptide Y and sympathetic neurotransmission
Ann. NY Acad. Sci.
Cited by (37)
The venous system during pregnancy. Part 1: physiologic considerations
2022, International Journal of Obstetric AnesthesiaCitation Excerpt :Sympathetic nerves are a major regulator of venous tone and capacitance,57 and the dense sympathetic innervation and high compliance of splanchnic compared with large conduit veins underscores their importance in hemodynamic regulation.57 Mesenteric veins are more sensitive than their arterial counterparts to adrenergic stimulation58–60 due to a higher density of α-adrenoceptors,61 differences in α-adrenoceptor expression,62 alterations in G-protein coupled receptor signaling,63 and the capacity of α-adrenoceptors to form heterodimers with other adrenoceptor subtypes.64,65 For example, α-1D and α-2C adrenoceptors interact within mesenteric veins but not arteries,66 with α-2 adrenoceptors exhibiting a more prominent role in constriction of veins than arteries and potentiating α-1 mediated constriction.62
Nerve growth factor facilitates redistribution of adrenergic and non-adrenergic non-cholinergic perivascular nerves injured by phenol in rat mesenteric resistance arteries
2016, European Journal of PharmacologyCitation Excerpt :Tyrosine hydroxylase (TH) is a rate-limiting enzyme for noradrenaline synthase and is contained in sympathetic adrenergic nerves, which act as vasoconstrictor nerves. TH-LI nerves have been shown to coexist with neuropeptide Y (NPY)-LI nerves in rat mesenteric arteries and skeletal muscle arteries of various kinds of animals, including rabbits, dogs, cats, and guinea pigs (Pernow et al., 1987; Smyth et al., 2000; Gradin et al., 2003). We previously reported that the in vivo topical application of phenol, which has been used to block peripheral nerve activity (Wang and Bukoski, 1999), on superior mesenteric arteries markedly reduced the distribution of sympathetic adrenergic NPY-containing nerves and CGRPergic nerves in rat mesenteric resistance arteries.
The purinergic neurotransmitter revisited: A single substance or multiple players?
2014, Pharmacology and TherapeuticsCitation Excerpt :The lack of EJPs in the vein implied that ATP is not involved in the junctional events in the veins and therefore is not released during nerve stimulation in the veins. However, a P2 receptor-mediated component in the contractile responses to EFS can be revealed in mesenteric vein isolated from reserpine-treated guinea-pigs (Smyth et al., 2000), suggesting that ATP and/or other purines are likely released upon action potential firings in both arteries and veins. Important answers to these questions were provided by the first direct measurements and quantitative comparison of nerve-evoked purine release in the two blood vessels (Bobalova & Mutafova-Yambolieva, 2001a) almost 20 years after the first observations that the mesenteric artery and vein differ in their electrical responses to nerve stimulation.
Functional crosstalk of prejunctional receptors on the modulation of noradrenaline release in mesenteric vessels: A differential study of artery and vein
2011, European Journal of PharmacologyCitation Excerpt :Arteries and veins play distinct roles in the maintenance of a proper circulatory dynamics (Kreulen, 2003) and differences in the sympathetic control of both types of vessels may contribute to blood flow regulation. In the veins sympathetic vasoconstriction is mainly mediated by noradrenaline, whereas in the arteries the co-transmitters ATP and neuropeptide Y also play an important role (Donoso et al., 1997; Smyth et al., 2000). Differences in the regulation of sympathetic neuronal activity may also contribute to the distinct roles of arteries and veins on the control of blood flow and volume distribution (Smyth et al., 2000; Bobalova and Mutafova-Yambolieva, 2001; Park et al., 2007).
Alterations in sympathetic neuroeffector transmission to mesenteric arteries but not veins in DOCA-salt hypertension
2010, Autonomic Neuroscience: Basic and Clinical