Abstract
The response to vasoactive agents of microvessels of the rat was tested in vivo by direct microscopic observation of the exteriorized mesentery and assessment of cutaneous vascular permeability changes with Evans blue. The constrictor response to a standard amount of noradrenaline in mesenteric microvessels was fully antagonized by acetylcholine in normal, diabetic, adrenalectomized and diabetic-adrenalectomized rats. In contrast, the minimum doses of histamine or bradykinin, effective in normal or adrenalectomized animals, had to be increased about 20 fold to be active in diabetic or diabetic-adrenalectomized animals. Topical application of insulin to mesenteric microvessels of diabetic animals, in amounts not causing any increase in serum insulin levels, improved or restored the capacity of the animals to respond to histamine or bradykinin, acting as antagonists of the vasoconstrictor response to noradrenaline. Topical insulin, however, was ineffective in normal animals given 2-deoxyglucose, the acute effects of which result from cellular glucopaenia unrelated to insulin deficiency. Vascular permeability responses to intracutaneous histamine or bradykinin were decreased in animals pretreated with 2-deoxyglucose as much as in diabetic animals. Pretreatment of normal animals with indomethacin produced no effect on the responses of these animals to histamine or bradykinin, tested as antagonists of noradrenaline on mesenteric microvessels, or as vascular permeability-increasing factors in the skin. Pretreatment of normal animals with chloroquine, mepacrine or dexamethasone had no effect on the reactivity of mesenteric microvessels to histamine and bradykinin, acting as antagonists to noradrenaline.(ABSTRACT TRUNCATED AT 250 WORDS)
Full text
PDF![635](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/1987095/8491ce6fa9b1/brjpharm00679-0032.png)
![636](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/1987095/cbd93ff35a3c/brjpharm00679-0033.png)
![637](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/1987095/09f185046871/brjpharm00679-0034.png)
![638](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/1987095/e8c6d4f66e18/brjpharm00679-0035.png)
![639](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/1987095/08f152caa3c1/brjpharm00679-0036.png)
![640](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/1987095/944d257472eb/brjpharm00679-0037.png)
![641](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/1987095/ac1d4696de9b/brjpharm00679-0038.png)
![642](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/1987095/e37e673adcae/brjpharm00679-0039.png)
![643](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/3d50/1987095/a04c14680965/brjpharm00679-0040.png)
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- ALKSNE J. F. The passage of colloidal particles across the dermal capillary wall under the influence of histamine. Q J Exp Physiol Cogn Med Sci. 1959 Jan;44(1):51–66. doi: 10.1113/expphysiol.1959.sp001376. [DOI] [PubMed] [Google Scholar]
- Authi K. S., Traynor J. R. Effects of antimalarial drugs on phospholipase A2 [proceedings]. Br J Pharmacol. 1979 Jul;66(3):496P–496P. [PMC free article] [PubMed] [Google Scholar]
- Blackwell G. J., Flower R. J., Nijkamp F. P., Vane J. R. Phospholipase A2 activity of guinea-pig isolated perfused lungs: stimulation, and inhibition by anti-inflammatory steroids. Br J Pharmacol. 1978 Jan;62(1):79–89. doi: 10.1111/j.1476-5381.1978.tb07009.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Chand N., Altura B. M. Acetylcholine and bradykinin relax intrapulmonary arteries by acting on endothelial cells: role in lung vascular diseases. Science. 1981 Sep 18;213(4514):1376–1379. doi: 10.1126/science.7268440. [DOI] [PubMed] [Google Scholar]
- De Mey J. G., Vanhoutte P. M. Heterogeneous behavior of the canine arterial and venous wall. Importance of the endothelium. Circ Res. 1982 Oct;51(4):439–447. doi: 10.1161/01.res.51.4.439. [DOI] [PubMed] [Google Scholar]
- Flower R. J., Blackwell G. J. The importance of phospholipase-A2 in prostaglandin biosynthesis. Biochem Pharmacol. 1976 Feb 1;25(3):285–291. doi: 10.1016/0006-2952(76)90216-1. [DOI] [PubMed] [Google Scholar]
- Fortes Z. B., Garcia Leme J., Scivoletto R. Influence of diabetes on the reactivity of mesenteric microvessels to histamine, bradykinin and acetylcholine. Br J Pharmacol. 1983 Jan;78(1):39–48. doi: 10.1111/j.1476-5381.1983.tb09360.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fortes Z. B., Garcia Leme J., Scivoletto R. Vascular reactivity in diabetes mellitus: role of the endothelial cell. Br J Pharmacol. 1983 Jul;79(3):771–781. doi: 10.1111/j.1476-5381.1983.tb10016.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Fox J., Galey F., Wayland H. Action of histamine on the mesenteric microvasculature. Microvasc Res. 1980 Jan;19(1):108–126. doi: 10.1016/0026-2862(80)90087-4. [DOI] [PubMed] [Google Scholar]
- Furchgott R. F., Zawadzki J. V. The obligatory role of endothelial cells in the relaxation of arterial smooth muscle by acetylcholine. Nature. 1980 Nov 27;288(5789):373–376. doi: 10.1038/288373a0. [DOI] [PubMed] [Google Scholar]
- Garcia-Leme J., Böhm G. M., Migliorini R. H., de Souza M. Z. Possible participation of insulin in the control of vascular permeability. Eur J Pharmacol. 1974 Dec;29(2):298–306. doi: 10.1016/0014-2999(74)90030-2. [DOI] [PubMed] [Google Scholar]
- Gordon J. L., Martin W. Stimulation of endothelial prostacyclin production plays no role in endothelium-dependent relaxation of the pig aorta. Br J Pharmacol. 1983 Sep;80(1):179–186. doi: 10.1111/j.1476-5381.1983.tb11064.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- KIPNIS D. M., CORI C. F. Studies of tissue permeability. V. The penetration and phosphorylation of 2-deoxyglucose in the rat diaphragm. J Biol Chem. 1959 Jan;234(1):171–177. [PubMed] [Google Scholar]
- King E. J., Garner R. J. The Colorimetric Determination of Glucose. J Clin Pathol. 1947 Nov;1(1):30–33. doi: 10.1136/jcp.1.1.30. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Leme J. G., Hamamura L., Migliorini R. H., Leite M. P. Influence of diabetes upon the inflammatory response of the rat. A pharmacological analysis. Eur J Pharmacol. 1973 Jul;23(1):74–81. doi: 10.1016/0014-2999(73)90246-x. [DOI] [PubMed] [Google Scholar]
- Llorach M. A., Böhm G. M., Leme J. G. Decreased vascular reactions to permeability factors in experimental diabetes. Br J Exp Pathol. 1976 Dec;57(6):747–754. [PMC free article] [PubMed] [Google Scholar]
- MAJNO G., PALADE G. E. Studies on inflammation. 1. The effect of histamine and serotonin on vascular permeability: an electron microscopic study. J Biophys Biochem Cytol. 1961 Dec;11:571–605. doi: 10.1083/jcb.11.3.571. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Morris H. R., Piper P. J., Taylor G. W., Tippins J. R. The effect of arachidonate lipoxygenase substrates and inhibitors on SRS-A release in the guinea-pig lung [proceedings]. Br J Pharmacol. 1979 Jul;66(3):452P–452P. [PMC free article] [PubMed] [Google Scholar]
- Osterby R., Gundersen H. J., Christensen N. J. The acute effect of insulin on capillary endothelial cells. Diabetes. 1978 Jul;27(7):745–749. doi: 10.2337/diab.27.7.745. [DOI] [PubMed] [Google Scholar]
- Van de Voorde J., Leusen I. Vascular endothelium and the relaxation effect of histamine on aorta of the rat. Arch Int Pharmacodyn Ther. 1982 Apr;256(2):329–330. [PubMed] [Google Scholar]
- Vargaftig B. B., Hai N. D. Selective inhibition by mepacrine of the release of "rabbit aorta contracting substance" evoked by the administration of bradykinin. J Pharm Pharmacol. 1972 Feb;24(2):159–161. doi: 10.1111/j.2042-7158.1972.tb08953.x. [DOI] [PubMed] [Google Scholar]
- WICK A. N., DRURY D. R., NAKADA H. I., WOLFE J. B. Localization of the primary metabolic block produced by 2-deoxyglucose. J Biol Chem. 1957 Feb;224(2):963–969. [PubMed] [Google Scholar]
- WILHELM D. L., MILL P. J., SPARROW E. M., MACKAY M. E., MILES A. A. Enzyme-like globulins from serum reproducing the vascular phenomena of inflammation. IV. Activable permeability factor and its inhibitor in the serum of the rat and the rabbit. Br J Exp Pathol. 1958 Jun;39(3):228–250. [PMC free article] [PubMed] [Google Scholar]
- Wallach D. P., Brown V. J. Studies on the arachidonic acid cascade--I. Inhibition of phospholipase A2 in vitro and in vivo by several novel series of inhibitor compounds. Biochem Pharmacol. 1981 Jun 1;30(11):1315–1324. doi: 10.1016/0006-2952(81)90315-4. [DOI] [PubMed] [Google Scholar]
- Williams J. R., Harrison T. R., Grollman A. A SIMPLE METHOD FOR DETERMINING THE SYSTOLIC BLOOD PRESSURE OF THE UNANESTHETIZED RAT. J Clin Invest. 1939 May;18(3):373–376. doi: 10.1172/JCI101051. [DOI] [PMC free article] [PubMed] [Google Scholar]