Effects of short- and long-term sympathectomy on vasoconstrictor responses of the rat mesenteric arterial bed.
1. The effects of short- and long-term sympathectomy were evaluated on vasoconstrictor function of constantly perfused mesenteric arterial beds isolated from rats: the effects of short-term sympathectomy were assessed at 3 and 8 days after 6-hydroxydopamine (6-OHDA) treatment of adult rats; the effects of long-term sympathectomy were assessed in adult rats treated at youth with guanethidine. 2. The relative degree of residual sympathetic innervation of the mesenteric arterial preparations was assessed by responses to electrical field stimulation (EFS; 16 Hz, 1 ms, 90 V, 30 s). Control responses were 95.6 +/- 3.9 mmHg (n = 35). Responses after sympathectomy were: 3 days after 6-OHDA, 2.9 +/- 0.9 mmHg (n = 15) < 8 days after 6-OHDA, 14.1 +/- 2.1 mmHg (n = 14) < guanethidine, 21.1 +/- 4.1 mmHg (n = 16). 3. Three days after 6-OHDA treatment there was an increase in the sensitivities of response to vasopressin and endothelin, producing leftward shifts of the dose-response curves of 0.66 +/- 0.11 and 0.88 +/- 0.13 log units respectively (n = 7-11), and a small increase in sensitivity of responses to noradrenaline (NA) and ATP. The maximal response to 5-hydroxytryptamine (5-HT) was increased. In contrast, there was a decrease in maximal constriction to NA and to the alpha 1-adrenoceptor agonist methoxamine. The alpha 2-adrenoceptor agonist clonidine did not elicit vasoconstriction at basal tone. There was no difference in vasodilator responses to the beta-adrenoceptor agonist isoprenaline in preparations with tone raised with prostaglandin F2 alpha (PGF2 alpha; 0.1-0.3 microM). 4. Eight days after 6-OHDA sympathectomy there was no significant difference in sensitivities or maximal responses to ATP, vasopressin and endothelin, but a small increase in the sensitivity of responses to 5-HT. Maximal responses to NA and methoxamine were significantly lower than the controls, but sensitivities were similar. There was no significant difference in vasodilator responses to isoprenaline in PGF2 alpha-raised tone preparations. 5. After long-term guanethidine sympathectomy maximal responses to 5-HT and NA were significantly reduced. Responses to ATP, vasopressin and endothelin were unchanged. 6. In mesenteric arterial preparations from untreated rats, ouabain (0.1 mM), a blocker of the Na+/K+ pump, significantly augmented the sensitivity and maximal responses to EFS, NA, methoxamine and 5-HT. Responses to ATP, vasopressin and endothelin were unaffected. 7. It is concluded that in the rat mesenteric arterial bed, short-term sympathectomy, where only 3% of the sympathetic nerve-mediated response remained, results in non-uniform changes in sensitivity and maximal responses to different vasoconstrictors, which cannot be entirely explained by changes in the Na+/K+ pump. Most of these changes disappeared at 8 days after 6-OHDA treatment, when nerve-mediated responses had partially returned. After long-term guanethidine sympathectomy, there was little change in responses to vasoconstrictors, and nerve-mediated responses were reduced to 22%. Although the variable factors are complex, it appears that in general, changes in responses of smooth muscle to vasoconstrictor substances after sympathetic denervation only occur if there is near-complete loss of nerve-mediated responses.
Ralevic
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V
Department of Anatomy and Developmental Biology, University College London.
Burnstock
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G
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000318:Adrenergic beta-Agonists / Q000494:pharmacology; D000818:Animals; D002316:Cardiotonic Agents / Q000494:pharmacology; D006145:Guanethidine; D066298:In Vitro Techniques; D008297:Male; D008638:Mesenteric Arteries / Q000187:drug effects / Q000294:innervation / Q000502:physiology*; D010042:Ouabain / Q000494:pharmacology; D016627:Oxidopamine; D051381:Rats; D017207:Rats, Sprague-Dawley; D000254:Sodium-Potassium-Exchanging ATPase / Q000187:drug effects / Q000378:metabolism; D013563:Sympathectomy, Chemical; D013565:Sympatholytics; D013997:Time Factors; D014661:Vasoconstriction / Q000187:drug effects / Q000502:physiology*
D000316:Adrenergic alpha-Agonists; D000318:Adrenergic beta-Agonists; D002316:Cardiotonic Agents; D013565:Sympatholytics; D010042:Ouabain; D016627:Oxidopamine; D000254:Sodium-Potassium-Exchanging ATPase; D006145:Guanethidine