Abstract
To analyze newborn cerebrovascular autoregulation, middle cerebral arteries from 3-4-d-old piglets were cannulated, and diameter changes after transmural pressure variation were measured. After an equilibration period at 30 mm Hg, pressure was modified from 10 to 70 mm Hg in 20-mm Hg steps. Segments with endothelium showed vasodilation during pressure decrease and vasoconstriction during pressure increase. In each case the maximum response was about 5% that of the resting diameter. Segments without endothelium responded passively to pressure change. Vasodilation during pressure decrease was reduced by the preferential calcium-activated potassium (KCa) channel blocker, tetraethylammonium (1 mM), and was absent with the nitric oxide (NO) synthase inhibitor NG-nitro-L-arginine methylester (L-NAME, 10 µM). The NO synthase substrate, L-arginine (10µM), counteracted the dilation blockade caused by L-NAME. The cyclooxygenase inhibitor indomethacin (10 µM) and the endothelin A receptor antagonist BQ-123 (10 µM) eliminated the pressure increase-induced vasoconstriction. The ATP-sensitive potassium channel blocker, glibenclamide (1 µM), and the endothelin B receptor antagonist, BQ-788 (10 nM), did not modify the autoregulatory response. None of these drugs modified the passive changes produced by pressure variations in segments without endothelium. These results suggest that: 1) piglet middle cerebral artery autoregulation is endothelium-dependent;2) NO and KCa channels are involved in vasodilation during transmural pressure decrease, and 3) endothelin-1, through endothelin A receptors, and prostanoids mediate vasoconstriction during pressure increase.
Similar content being viewed by others
Log in or create a free account to read this content
Gain free access to this article, as well as selected content from this journal and more on nature.com
or
Abbreviations
- ET:
-
endothelin
- KATP:
-
ATP-sensitive potassium
- KCa:
-
calcium-activated potassium
- L-NAME:
-
NG-nitro-L-arginine methylester
- MCA:
-
middle cerebral artery
- NE:
-
norepinephrine
- NO:
-
nitric oxide
- NOS:
-
NO synthase
- TEA:
-
tetraethylammonium
- TP:
-
transmural pressure
References
Volpe JJ 1989 Intraventricular hemorrhage and brain injury in the premature infant. Neuropathology and pathogenesis. Clin Perinatol 16: 361–386
Leffler CW, Busija DW, Beasley DG 1987 Effect of therapeutic dose of indomethacin on the cerebral circulation of newborn pigs. Pediatr Res 21: 188–192
Kontos HA, Wei EP, Navari RM, Levasseur JE, Rosenblum WI, Patterson JL 1978 Response of cerebral arteries and arterioles to acute hypotension and hypertension. Am J Physiol 234:H371–H383
Jackson PA, Duling BR 1989 Myogenic responses and wall mechanics of arterioles. Am J Physiol 257:H1147–H1155
Faraci FM 1991 Role of endothelium-derived relaxing factor in cerebral circulation: large arteries vs. microcirculation. Am J Physiol 261:H1038–H1042
Shimoda LA, Norins NA, Jeutter DC, Madden JA 1996 Flow-induced responses in piglet isolated cerebral arteries. Pediatr Res 39: 574–583
Tuor UI, Grewal D 1994 Autoregulation of cerebral blood flow: influence of local brain development and postnatal age. Am J Physiol 267:H2220–H2228
García-Roldán JL, Bevan JA 1990 Flow-induced constriction and dilation of cerebral resistance arteries. Circ Res 66: 1445–1448
Harder DR, Sánchez-Ferrer CF, Kauser K, Stekiel WJ, Rubanyi GM 1989 Pressure releases a transferable endothelial contractile factor in cat cerebral arteries. Circ Res 65: 193–198
Pearce WJ, Hull AD, Long DM, Longo LD 1991 Developmental changes in ovine cerebral artery composition and reactivity. Am J Physiol 261:R458–R465
Martínez-Orgado J, Salaices M, Rodríguez-Martínez MA, Sánchez-Ferrer CF, Marín J 1995 Age-related changes in nitric oxide-mediated vasodilation of cerebral arteries from newborn piglets. Pharm Sci 1: 35–37
Pearce WJ, Hull AD, Long DM, White CR 1994 Effects of maturation on cyclic GMP-dependent vasodilation in ovine basilar and carotid arteries. Pediatr Res 36: 25–33
Chemtob S, Beharry K, Rex J, Varna DR, Aranda JV 1990 Prostanoids determine the range of cerebral blood flow autoregulation in newborn piglets. Stroke 21: 777–784
Meadow W, Rudinsky B, Bell A, Lozon M, Randle C, Hipps R 1994 The role of prostaglandins and endothelium-derived relaxing factor in the regulation of cerebral blood flow and cerebral oxygen utilization in the piglet: operationalizing the concept of essential circulation. Pediatr Res 35: 649–656
Patel TR, McAuley MA, McCulloch J 1996 Endothelin receptor mediated vasoconstriction and dilation in feline cerebral arteriolesin vivo. Eur J Pharmacol 20: 41–48
Kitazono T, Faraci FM, Taguchi H, Heistad DD 1995 Role of potassium channels in cerebral blood vessels. Stroke 26: 1713–1723
Iadecola C, Pelligrino DA, Moskowitz MA, Lassen NA 1994 Nitric oxide synthase inhibition and cerebrovascular regulation. J Cereb Blood Flow Metab 14: 175–192
Buchanan JE, Phillis JW 1993 The role of nitric oxide in the regulation of cerebral blood flow. Brain Res 610: 248–255
Wang Q, Paulson OB, Lassen NA 1992 Is autoregulation of cerebral blood flow in rats influenced by nitro-L-arginine, a blocker of the synthesis of nitric oxide?. Acta Physiol Scand 145: 297–298
O'Neill JT, Sogn A, Hunt T, Palacino J 1995 Inhibition on nitric oxide synthase alters the cerebral blood flow response to hemorrhagic hypotension in piglets. Pediatr Res 37: 227A
Tanaka K, Fukuuchi Y, Gomi S, Mihara B, Shirai T, Nogawa S, Nozaki H, Nagata E 1993 Inhibition of nitric oxide synthesis impairs autoregulation of cerebral blood flow in the rat. Neuroreport 4: 267–270
Kobari M, Fukuuchi Y, Tomita M, Tanahashi N, Takeda H 1994 Role of nitric oxide in regulation of cerebral microvascular tone and autoregulation of cerebral blood flow in cats. Brain Res 667: 255–262
Norins NA, Wendelberger K, Hoffman RG, Keller PA, Madden JA 1992 Effects of indomethacin on myogenic contractile activation and responses to changes in O2 and CO2 in isolated feline cerebral arteries. J Cereb Blood Flow Metab 12: 866–872
Halpern W, Kelley M 1991 In vitro methodology for resistance arteries. Blood Vessels 28: 245–251
Norins NA, Madden JA 1992 Developmental changes in cerebral artery autoregulation in piglets. Pediatr Res 31: 214A
Pearce WJ, Ashwall S, Cuevas J 1989 Direct effects of graded hypoxia on intact and denuded rabbit cranial arteries. Am J Physiol 257:H824–H833
Liu Y, Harder DR, Lombard JH 1994 Myogenic activation of canine small renal arteries after nonchemical removal of endothelium. Am J Physiol 267:H302–H307
Eidson TH, Edrington JL, Albuquerque MLC, Zuckerman SL, Leffler CW 1995 Light/dye microvascular injury eliminates pial arteriolar dilation in hypotensive piglets. Pediatr Res 37: 10–14
Busija DW, Leffler CW 1991 Selective attenuation by perivascular blood of prostanoid-dependent cerebrovascular dilation in piglets. Stroke 22: 484–488
Harada J, Takaku A, Endo S, Kuwayama N, Fukuda O 1991 Differences in critical cerebral blood flow with age in swine. J Neurosurg 75: 103–107
Martínez-Orgado J, Salaices M, Rodríguez-Martínez MA, Sánchez-Ferrer CF, Marín J 1994 Role of nitric oxide on the endothelium-dependent vasodilation in newborn piglet cerebral arteries. Gen Pharmacol 25: 899–902
Traystman RJ, Moore LE, Helfaer MA, Davis S, Banasiak K, Williams M, Hurn P 1995 Nitro-L-arginine analogues. Dose- and time-related nitric oxide synthase inhibition in brain. Stroke 26: 864–869
Brayden JE, Nelson MT 1992 Regulation of arterial tone by activation of calcium-dependent potassium channels. Science 256: 532–535
Brayden JE 1990 Membrane hyperpolarization is a mechanism of endothelium-dependent cerebral vasodilation. Am J Physiol 259:H668–H673
Khan SA, Mathews R, Meisheri KD 1993 Role of calcium-activated K+ channels in vasodilation induced by nitroglycerine, acetylcholine and nitric oxide. J Pharmacol Exp Ther 267: 1327–1335
Robertson BE, Schubert R, Hescheler J, Nelson MT 1993 c-GMP-dependent protein kinase activates Ca-activated K channels in cerebral artery smooth muscle cells Am J Physiol 265:C299–C303
Armstead WM 1996 Role of ATP-sensitive K+ channels in cGMP-mediated pial artery vasodilation. Am J Physiol 270:H423–H426
Lee WS, Kwon Y, Yu SS, Rhim BY, Hong KW 1993 Disturbances in autoregulatory responses of rat pial arteries by sulfonylureas. Life Sci 52: 1527–1534
Leffler CW, Busija DW 1987 Prostanoids and pial arteriolar diameter in hypotensive newborn pigs. Am J Physiol 252:H687–H691
Karaki H, Sudjarwo SA, Hori M 1994 Novel antagonist of endothelin ETB1 and ETB2 receptors BQ-788: effects on blood vessel and small intestine. Biochem Biophys Res Commun 205: 168–173
Armstead WM, Mirro R, Leffler CW, Busija DW 1989 Influence of endothelin on piglet cerebral microcirculation. Am J Physiol 257:H707–H710
Acknowledgements
The authors thank George F. R. Marsden for correction and critical evaluation of the manuscript.
Author information
Authors and Affiliations
Additional information
Supported by grants from Direccion General de Industria, Ciencia y Technologia (PB94-0152), FIS (95/1954), Comunidad de Madrid (I+D 0017/94 and AE 00339/95), and Bayer España. This work is ascribed to Biomed Project No. BMH1-CT94-1375 of the European Economic Community.
Rights and permissions
About this article
Cite this article
Martínez-Orgado, J., González, R., Alonso, M. et al. Endothelial Factors and Autoregulation during Pressure Changes in Isolated Newborn Piglet Cerebral Arteries. Pediatr Res 44, 161–167 (1998). https://doi.org/10.1203/00006450-199808000-00004
Received:
Accepted:
Issue date:
DOI: https://doi.org/10.1203/00006450-199808000-00004
This article is cited by
-
Cannabidiol reduces lipopolysaccharide-induced vascular changes and inflammation in the mouse brain: an intravital microscopy study
Journal of Neuroinflammation (2011)
