Effects of norepinephrine on the oxidative pentose phosphate pathway in the rat heart.
To examine whether stimulation of alpha-adrenergic receptors may affect the oxidative pentose phosphate pathway (PPP) in the rat heart, norepinephrine (NE) and the alpha-adrenergic agonist norfenephrine were used. NE was administered as a continuous intravenous infusion in awake rats for 3 days. It stimulated the activity of cardiac glucose-6-phosphate dehydrogenase (G-6-PD), the first and regulating enzyme of the oxidative PPP, in a dose-dependent manner. With the highest dose (0.2 mg.kg-1.hr-1), there was also a time-dependent enhancement. The increase observed after 48 hours was attenuated partially by the beta-receptor blocker metoprolol and the alpha-receptor blocker prazosin. It was entirely abolished when both drugs were administered. Carvedilol, a beta-adrenergic blocker and vasodilator with alpha 1-blocking activity (0.5 mg.kg-1.hr-1), prevented the NE-induced increase in cardiac G-6-PD activity, in functional parameters (heart rate, left ventricular systolic pressure, and left ventricular dP/dtmax), and in the heart weight/body weight ratio. The alpha-adrenergic stimulator norfenephrine increased myocardial G-6-PD activity; prazosin prevented this stimulation. NE and norfenephrine also elevated the available pool of cardiac 5-phosphoribosyl-1-pyrophosphate. G-6-PD activity was enhanced in cardiac myocytes freshly isolated from the left ventricle of rats that had received NE infusion for 3 days (12.3 +/- 1.4 units/g protein) compared with control rats (1.5 +/- 0.4 units/g protein). The activity of 6-phosphogluconate dehydrogenase, one of the enzymes in the oxidative PPP, was elevated only moderately from 12.7 +/- 0.7 to 19.1 +/- 1.4 units/g protein. Combined alpha- and beta-receptor blockade with carvedilol attenuated these effects.(ABSTRACT TRUNCATED AT 250 WORDS)
Zimmer
H G
HG
Department of Physiology, University of Munich, FRG.
Lankat-Buttgereit
B
B
Kolbeck-Rühmkorff
C
C
Nagano
T
T
Zierhut
W
W
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000818:Animals; D015152:Blotting, Northern; D002227:Carbazoles / Q000494:pharmacology; D000077261:Carvedilol; D005260:Female; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006321:Heart / Q000187:drug effects* / Q000502:physiology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D008790:Metoprolol / Q000494:pharmacology; D009206:Myocardium / Q000166:cytology / Q000201:enzymology / Q000378:metabolism*; D009638:Norepinephrine / Q000494:pharmacology*; D009693:Nucleic Acid Hybridization; D010427:Pentose Phosphate Pathway / Q000187:drug effects*; D011412:Propanolamines / Q000494:pharmacology; D012313:RNA / Q000032:analysis; D051381:Rats; D011919:Rats, Inbred Strains
D000319:Adrenergic beta-Antagonists; D002227:Carbazoles; D011412:Propanolamines; D000077261:Carvedilol; D012313:RNA; D005954:Glucosephosphate Dehydrogenase; D008790:Metoprolol; D009638:Norepinephrine