title: Angiotensin-induced enhancement of excitatory junction potentials evoked by periarteriolar nerve stimulation and vasoconstriction in rat mesenteric arteries are both mediated by the angiotensin AT1 receptor.
abstract: The aims of the present study were to determine the angiotensin II (AngII) receptor subtype(s) involved in vasoconstriction and enhancement of sympathetic neurotransmission in rat isolated mesenteric arteries. Vasoconstriction was assessed in mesenteric artery ring preparations suspended under 0.5 g of tension in a myograph. In control arteries, with an intact endothelium, AngII (1 nmol/l-3 micromol/l) caused a concentration-dependent contraction. The pEC(50) for AngII was 7.6 +/- 0.2 and the maximum response of 0.24 +/- 0.07 g was reached with 100 nmol/l. In the presence of indomethacin (3.0 micromol/l) and N(omega)-nitro-L-arginine (NOLA) (100 micromol/l) to remove the influence of endothelium-derived prostaglandins and nitric oxide, the maximum response evoked by AngII was increased to 0.48 +/- 0.1 g and the pEC(50) was 7.6 +/- 0.3. The AT1 receptor antagonist losartan (30 nmol/l) competitively blocked the AngII-induced contractions with an estimated pA(2) of 8.2 in both the control arteries and in arteries treated with indomethacin and NOLA. The AT2 receptor antagonist PD 123319 (1 micromol/l) did not affect AngII-induced contractions under either condition. Conventional intracellular microelectrode recording techniques were used to investigate the effects of AngII on excitatory junction potentials (EJP) evoked by stimulation of periarteriolar sympathetic nerves. Stimulation with trains of 10 pulses delivered at 0.9 Hz evoked EJP which were blocked by tetrodotoxin (0.1 micromol/l), guanethidine (30 micromol/l) and the P(2X) receptor desensitizing agent alpha,beta-methylene ATP (30 micromol/l) suggesting the EJP were mediated by ATP, or a related purine, released from sympathetic nerves. AngII (0.3- 100 nmol/l) did not affect the resting membrane potential or the amplitude of the first EJP, but did enhance the amplitude of the plateau EJP later in the train. A maximum 49.2 +/- 3.9% enhancement of the plateau EJP amplitude was elicited by 10 nmol/l AngII and the pEC(50) was 9.1 +/- 0.1. The facilitatory effect of AngII on EJP amplitude was not altered in the presence of indomethacin and NOLA. Losartan (30 nmol/l) competitively blocked the AngII-induced enhancement of plateau EJP amplitude, with an estimated pA(2) of 8.6. PD 123319 did not alter the enhancement of plateau EJP amplitude by AngII. The results from the present study show that both the vasoconstriction and enhancement of plateau EJP amplitude by AngII in rat mesenteric arteries are blocked by the AT1 receptor antagonist losartan and are unaffected by the AT2 receptor antagonist PD 123319.
authors.affiliation: Department of Pharmacology, University of Melbourne, Parkville, Victoria, Australia. j.ziogas@pharmacology.unimelb.edu.au
authors.forename: J
authors.initials: J
authors.lastname: Ziogas
authors.forename: K
authors.initials: K
authors.lastname: Vessey
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001160:Arterioles / Q000187:drug effects / Q000502:physiology; D004558:Electric Stimulation; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin / Q000502:physiology*; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D057911:Angiotensin Receptor Antagonists; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D011945:Receptors, Angiotensin; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D019808:Losartan