Vascular CO Counterbalances the Sensitizing Influence of 20-HETE on Agonist-Induced Vasoconstriction

• Published in: Hypertension (Dallas, Tex. 1979) Vol. 44; no. 2; pp. 210 - 216
• Main Authors: Kaide, Jun-Ichi, Zhang, Fan, Wei, Yuan, Wang, WenHui, Gopal, Venkat Raj, Falck, John R, Laniado-Schwartzman, Michal, Nasjletti, Alberto
• Format: Journal Article
• Language: English
• Published: Philadelphia, PA American Heart Association, Inc 01.08.2004; Hagerstown, MD Lippincott
• Subjects: Adrenergic Agonists - pharmacology; Animals; Arterial hypertension. Arterial hypotension; Arteries - drug effects; Arteries - metabolism; Biological and medical sciences; Blood and lymphatic vessels; Blood vessels and receptors; Carbon Monoxide - metabolism; Cardiology. Vascular system; Dose-Response Relationship, Drug; Experimental diseases; Fundamental and applied biological sciences. Psychology; Hydroxyeicosatetraenoic Acids - pharmacology; In Vitro Techniques; Male; Medical sciences; Muscle, Smooth, Vascular - drug effects; Muscle, Smooth, Vascular - metabolism; Patch-Clamp Techniques; Phenylephrine - pharmacology; Potassium Channels - metabolism; Rats; Rats, Sprague-Dawley; Renal Artery; Renal Circulation; Vasoconstriction; Vasopressins - pharmacology; Vertebrates: cardiovascular system; Hypertension; renal circulation; Cardiovascular disease; Inorganic element; Vasopressin; HETE; vasopressins; Induced vasoconstriction; potassium channels; Carbon monoxide; Adrenergic receptor; Potassium; adrenergic receptor agonists
• ISSN: 0194-911X; 1524-4563
• DOI: 10.1161/01.HYP.0000135658.57547.bb

We examined the influence of interactions between CO and 20-hydroxyeicosatetraenoic acid (20-HETE) on vascular reactivity to phenylephrine and vasopressin. Renal interlobar arteries incubated in Krebs buffer released CO at a rate that is decreased (from 125.0±15.2 to 46.3±8.8 pmol/mg protein per hour, P <0.05) by the heme oxygenase inhibitor chromium mesoporphyrin (CrMP; 30 μmol/L). The level of 20-HETE in vessels was not affected by CrMP (74.3±6.1 versus 72.5±16.2 pmol/mg protein), but was decreased (P <0.05) by CO (1 μmol/L; 33.2±7.9 pmol/mg protein) or the cytochrome P450 – 4A inhibitor N-methylsulfonyl-12,12-dibromododec-11-enamide (DDMS; 30 μmol/L; 11.4±3.3 pmol/mg protein). Phenylephrine elicited development of isometric tension in vascular rings mounted on a wire-myograph (EC50, 0.29±0.02 μmol/L; Rmax, 3.78±0.19 mN/mm). The sensitivity to phenylephrine was decreased (P <0.05) by CO (1 μmol/L; EC50, 0.60±0.04 μmol/L) or DDMS (EC50, 0.71±0.12 μmol/L) and increased (P <0.05) by 20-HETE (10 μmol/L; EC50, 0.08±0.02 μmol/L) or CrMP (EC50, 0.11±0.02 μmol/L). Notably, neither CO nor CrMP changed the sensitivity to phenylephrine in vessels treated with DDMS. Refractoriness to CO and CrMP in such a setting was eliminated by inclusion of 20-HETE (1 μmol/L) in the bathing buffer. The aforementioned interventions affected the vascular reactivity to vasopressin in a similar manner. These data indicate that the reactivity of renal arteries to phenylephrine and vasopressin is reciprocally influenced by CO and 20-HETE of vascular origin and that CO desensitizes the vascular smooth muscle to constrictor agonists by interfering with the sensitizing influence of 20-HETE.