Enhancement by exogenous and locally generated angiotensin II of purinergic neurotransmission via angiotensin type 1 receptor in the guinea-pig isolated mesenteric artery.
1. Angiotensin II is known to enhance sympathetic neurotransmission in the vasculature by increasing the release of noradrenaline, but little is known about the effect on the co-released transmitter, adenosine 5'-triphosphate (ATP). In the present study we have examined the effect of angiotensin II on the excitatory junction potential (e.j.p.) elicited by repetitive field stimulation in the guinea-pig isolated mesenteric artery, to establish the angiotensin II receptor subtype involved in modulating the release of ATP and the role of the endothelium in converting angiotensin I to angiotensin II. 2. Suramin (300 microM), a P2 purinoceptor antagonist, abolished both the e.j.p.s and depolarizing response to alpha,beta-methylene-ATP, a stable analogue of ATP, without affecting the resting membrane potential and noradrenaline-induced depolarization. 3. Angiotensin II (0.1 microM) affected neither the resting membrane potential nor the amplitude of the first e.j.p., but increased the amplitudes of the subsequent e.j.p.s. This enhancing effect of angiotensin II was abolished by CV-11974 (0.1 microM), an angiotensin II type 1 (AT1) receptor antagonist, but unaffected by PD 123319 (1 microM), an angiotensin II type 2 (AT2) receptor antagonist, or CGP 42112A (1 microM), AT2 receptor ligand. 4. Angiotensin I (0.1 microM) exerted a similar effect on e.j.p.s to that of angiotensin II. CV-11974 (0.1 microM) or temocaprilat (10 microM), an angiotensin converting enzyme (ACE) inhibitor, abolished the effect of angiotensin I. Removal of the endothelium did not alter the action of angiotensin I. 5. The results of the present study indicate that the release of ATP from sympathetic nerves innervating the guinea-pig isolated mesenteric artery, as determined from the magnitude of the e.j.p., can be enhanced by angiotensin II via activation of prejunctional AT1 receptors. Qualitatively similar effects were observed with angiotensin I, which appears to be converted into angiotensin II by a subendothelial process.
Onaka
U
U
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Fujii
K
K
Abe
I
I
Fujishima
M
M
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology; D000803:Angiotensin I / Q000378:metabolism / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology / Q000502:physiology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology; D001713:Biphenyl Compounds; D004558:Electric Stimulation; D005071:Evoked Potentials / Q000187:drug effects; D005260:Female; D006168:Guinea Pigs; D007093:Imidazoles / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D009842:Oligopeptides / Q000494:pharmacology; D058919:Purinergic P2 Receptor Antagonists; D011725:Pyridines / Q000494:pharmacology; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin / Q000187:drug effects / Q000502:physiology*; D013498:Suramin / Q000494:pharmacology; D009435:Synaptic Transmission / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology; D014662:Vasoconstrictor Agents / Q000494:pharmacology
D000806:Angiotensin-Converting Enzyme Inhibitors; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D007093:Imidazoles; D009842:Oligopeptides; D058919:Purinergic P2 Receptor Antagonists; D011725:Pyridines; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; C060894:CGP 42112A; C073402:PD 123319; D013498:Suramin; D000255:Adenosine Triphosphate; D000803:Angiotensin I; C002630:alpha,beta-methyleneadenosine 5'-triphosphate; C081643:candesartan