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(Circulation Research. 2001;89:648.)
© 2001 American Heart Association, Inc.

Editorials

EDHF and NO

Different Pathways for Production—Similar Actions

William M. Chilian, Ryoji Koshida

From the Department of Physiology and Cardiovascular Center, Medical College of Wisconsin, Milwaukee, Wis.

Correspondence to William M. Chilian, PhD, Department of Physiology, Cardiovascular Center, 8701 Watertown Plank Rd, Milwaukee, WI 53226-0509. E-mail chilian@mcw.edu

Key Words: nitric oxide • endothelium-derived hyperpolarizing factor • vasodilation • endothelium

In this issue of Circulation Research, Véquaud and Thorin¹ present observations that attest to differential G protein signaling in dilation to nitric oxide (NO) and endothelium-derived hyperpolarization factor (EDHF). The investigators also report that EDHF of the mesenteric artery is not a metabolite of phospholipase C, which strongly suggests that this vasodilator is not a lipid metabolite of cytochrome P450. Véquaud and Thorin also reported that EDHF-mediated dilation is calcium independent, which contrasts to the calcium dependency of agonist-induced NO-mediated dilation. And finally the authors report that heat shock protein 90 (Hsp90) participates in the production of NO but not EDHF. This study not only provides important contributions to our understanding of NO- and EDHF-mediated vasodilation but also presents a methodological tour de force in the study of microvascular signaling using the intracellular application of antibodies as specific inhibitors of the signaling pathways.

With regard to the methodological advance, the authors’ method for the study of signaling pathways in intact microvessels is novel and is based on a technique described to study transduction pathways in cultured cells.² Specifically, antibodies to specific G proteins or Hsp90 were incorporated into the endothelium of isolated pressurized microvessels using osmotic shock—hyperosmotic conditions followed by hypoosmotic shock. After this treatment, the nonspecific effects appeared nonexistent as evidenced by restoration of spontaneous tone and myogenic responses. The advantage of this approach is that the effects of an antibody should be specific. This contrasts to the application of so-called "specific" inhibitors of enzymes—most of these inhibitors . . . [Full Text of this Article]

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