Subarachnoid hemorrhage and endothelial L-arginine pathway in small brain stem arteries in dogs

Zvonimir S Katusic, J. H. Milde, F. Cosentino, B. S. Mitrovic, F. M. Faraci

Research output: Contribution to journalArticle

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Abstract

Background and Purpose: Experiments were designed to determine the effect of subarachnoid hemorrhage on endothelium-dependent relaxations in small arteries of the brain stem. A 'double-hemorrhage' canine model of the disease was used, and the presence of vasospasm in the basilar artery was confirmed by angiography. Methods: Secondary branches of both untreated basilar arteries (inner diameter, 324±11 μm; n=12) and arteries exposed to subarachnoid hemorrhage for 7 days (inner diameter, 328±12 μm; n=12) were dissected and mounted on glass microcannulas in organ chambers. Changes in the intraluminal diameter of pressurized arteries were measured using a video dimension analyzer. Results: In untreated arteries, 10-11 to 10-7 M vasopressin, 10-10 to 10-6 M bradykinin, and 10-9 to 10-6 M calcium ionophore A23187 caused endothelium-dependent relaxations. At 10-6 and 3 x 10-4 M the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) abolished relaxations to vasopressin and produced small but significant rightward shifts of the concentration-response curves to bradykinin and A23187. At 10-3 M L-arginine prevented the inhibitory effect of L-NAME. Subarachnoid hemorrhage abolished relaxations to vasopressin but did not affect relaxations to bradykinin or A23187. Conclusions: These studies suggest that in small arteries of the brain stem vasopressin causes relaxations by activation of the endothelial L-arginine pathway. This mechanism of relaxation is selectively inhibited by subarachnoid hemorrhage. Preservation of endothelium-dependent relaxations to bradykinin and A23187 is consistent with the concept that small arteries are resistant to vasospasm after subarachnoid hemorrhage.

Original languageEnglish (US)
Pages (from-to)392-399
Number of pages8
JournalStroke
Volume24
Issue number3
StatePublished - 1993

Fingerprint

Subarachnoid Hemorrhage
Brain Stem
Arginine
Arteries
Calcimycin
Bradykinin
Dogs
Vasopressins
NG-Nitroarginine Methyl Ester
Endothelium
Basilar Artery
Dog Diseases
Calcium Ionophores
Nitric Oxide Synthase
Glass
Angiography
Hemorrhage

Keywords

  • brain stem
  • dogs
  • nitric oxide
  • vasospasm

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Neuroscience(all)

Cite this

Katusic, Z. S., Milde, J. H., Cosentino, F., Mitrovic, B. S., & Faraci, F. M. (1993). Subarachnoid hemorrhage and endothelial L-arginine pathway in small brain stem arteries in dogs. Stroke, 24(3), 392-399.

Subarachnoid hemorrhage and endothelial L-arginine pathway in small brain stem arteries in dogs. / Katusic, Zvonimir S; Milde, J. H.; Cosentino, F.; Mitrovic, B. S.; Faraci, F. M.

In: Stroke, Vol. 24, No. 3, 1993, p. 392-399.

Research output: Contribution to journalArticle

Katusic, ZS, Milde, JH, Cosentino, F, Mitrovic, BS & Faraci, FM 1993, 'Subarachnoid hemorrhage and endothelial L-arginine pathway in small brain stem arteries in dogs', Stroke, vol. 24, no. 3, pp. 392-399.
Katusic, Zvonimir S ; Milde, J. H. ; Cosentino, F. ; Mitrovic, B. S. ; Faraci, F. M. / Subarachnoid hemorrhage and endothelial L-arginine pathway in small brain stem arteries in dogs. In: Stroke. 1993 ; Vol. 24, No. 3. pp. 392-399.
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AB - Background and Purpose: Experiments were designed to determine the effect of subarachnoid hemorrhage on endothelium-dependent relaxations in small arteries of the brain stem. A 'double-hemorrhage' canine model of the disease was used, and the presence of vasospasm in the basilar artery was confirmed by angiography. Methods: Secondary branches of both untreated basilar arteries (inner diameter, 324±11 μm; n=12) and arteries exposed to subarachnoid hemorrhage for 7 days (inner diameter, 328±12 μm; n=12) were dissected and mounted on glass microcannulas in organ chambers. Changes in the intraluminal diameter of pressurized arteries were measured using a video dimension analyzer. Results: In untreated arteries, 10-11 to 10-7 M vasopressin, 10-10 to 10-6 M bradykinin, and 10-9 to 10-6 M calcium ionophore A23187 caused endothelium-dependent relaxations. At 10-6 and 3 x 10-4 M the nitric oxide synthase inhibitor N(G)-nitro-L-arginine methyl ester (L-NAME) abolished relaxations to vasopressin and produced small but significant rightward shifts of the concentration-response curves to bradykinin and A23187. At 10-3 M L-arginine prevented the inhibitory effect of L-NAME. Subarachnoid hemorrhage abolished relaxations to vasopressin but did not affect relaxations to bradykinin or A23187. Conclusions: These studies suggest that in small arteries of the brain stem vasopressin causes relaxations by activation of the endothelial L-arginine pathway. This mechanism of relaxation is selectively inhibited by subarachnoid hemorrhage. Preservation of endothelium-dependent relaxations to bradykinin and A23187 is consistent with the concept that small arteries are resistant to vasospasm after subarachnoid hemorrhage.

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