Faculty Collaboration Database

Cerebral blood flow during inhibition of brain nitric oxide synthase activity in normal, hypertensive, and stroke-prone rats. Stroke 1995 Jun;26(6):1079-85

Date

06/01/1995

Pubmed ID

7539167

DOI

10.1161/01.str.26.6.1079

Scopus ID

2-s2.0-0029016092 (requires institutional sign-in at Scopus site)   22 Citations

Abstract

BACKGROUND AND PURPOSE: Because tonic production of nitric oxide (NO) is important in regulating cerebrovascular tone and NO may be important in the mechanism of brain injury from focal ischemia, we speculated that stroke predisposition in spontaneously hypertensive stroke-prone rats (SHR-SP) may be related to impaired tonic production of NO. This study was designed to test the hypothesis that the cerebral blood flow (CBF) response to inhibition of NO synthase in SHR-SP would be different than that observed in normal Wistar-Kyoto (WKY) rats and non-stroke-prone spontaneously hypertensive rats (SHR).

METHODS: Pentobarbital-anesthetized, mechanically ventilated rats were tested for CBF response to saline, 5 or 20 mg/kg IV of NG-monomethyl-L-arginine (L-NMMA), or 20 mg/kg IV of N omega-nitro-L-arginine (L-NA). In addition, specificity for an NO-dependent mechanism was assessed by determining the ability to reverse any alteration in CBF with L-arginine. Hemorrhage was used to minimize any increase in mean arterial blood pressure (MABP) from NO synthase inhibition. In a separate cohort of rats, differential sensitivity of NO synthase for inhibition by nitro-arginine analogues was determined.

RESULTS: Baseline MABP was greater in SHR-SP (185 +/- 3, n = 38) and SHR (169 +/- 3, n = 38) compared with WKY rats (101 +/- 2 mm Hg, n = 38, P < .05). Baseline CBF was similar between strains; however, cerebrovascular resistance was higher in SHR-SP (2.16 +/- 0.09, n = 27) and SHR (1.94 +/- 0.07, n = 27) compared with WKY rats (1.23 +/- 0.06 mm Hg/mL per minute per 100 g, n = 27, P < .05). CBF was unchanged with 5 mg/kg L-NMMA or with L-arginine in the absence of L-NMMA in each strain. CBF decreased similarly in SHR and SHR-SP (n = 9 each) in response to 20 mg/kg L-NMMA (SHR, 85 +/- 6 to 67 +/- 6; SHR-SP, 87 +/- 7 to 69 +/- 5 mL/min per 100 g) and was completely reversed by L-arginine. CBF did not decrease with 20 mg/kg L-NMMA in WKY rats. Administration of L-NA (n = 5 each) produced similar reduction of CBF (WKY rats, 67 +/- 6%; SHR, 49 +/- 9%; SHR-SP, 61 +/- 6% of baseline) and inhibition of NO synthase in each strain (approximately 80% inhibition).

CONCLUSIONS: There was no difference in the cerebrovascular response to NO synthase inhibition in SHR-SP and non-stroke-prone SHR. Therefore, it is unlikely that an altered sensitivity of NO synthase to inhibition can explain predisposition to stroke in SHR-SP.

Author List

Izuta M, Clavier N, Kirsch JR, Traystman RJ

MESH terms used to index this publication - Major topics in bold

Amino Acid Oxidoreductases
Animals
Arginine
Blood Pressure
Brain
Cerebrovascular Circulation
Female
Male
Nitric Oxide Synthase
Nitroarginine
Rats
Rats, Inbred SHR
Rats, Inbred WKY
Reference Values
Regional Blood Flow
Species Specificity
Structure-Activity Relationship
Vascular Resistance
omega-N-Methylarginine