Korean J Physiol Pharmacol.  1998 Feb;2(1):63-68.

Changes in cytosolic Ca2+ but not in cGMP contents may be more important to nitric oxide-mediated relaxation in depolarized vascular smooth muscle

• Lee HS
• Chang KC

Abstract

Nitric oxide (NO)-mediated relaxation in vascular smooth muscle involves not only activation of guanylate cyclase but also hyperpolarization of the membrane. It has been shown that depolarization decreases the (Ca2+) sensitivity of myosin light chain kinase in arterial smooth muscle, and nitric oxide (NO)-mediated relaxation was attenuated in this situation. However, why potassium inhibits or attenuates the action of EDRF/NO is not clear. Therefore, we investigated the magnitude of relaxation and cGMP contents using measures known to release NO, such as photorelaxation, photo activated NO-mediated relaxation, and NO-donor (SNP)-mediated relaxation in porcine coronary arterial rings in which contractile conditions were made by different degree of depolarization, i.e., contraction in response to U46619 or U46619 plus KCl. In all cases, the magnitude of relaxation was significantly greater (P<0.05) in U46619-contracted rings than in U46619+KCl-contracted ones. Although accumulation of cGMP was evident with three measures employed in the present study, no difference was found in cGMP contents between U46619 and U46619+KCl conditions, indicating that the diminished relaxation in KCl containing solution is cGMP-independent mechanism(s). To understand this further, cytosolic Ca2+ changes due to NO were compared in rat thoracic aorta by exploiting photoactivated NO using streptozotocin (STZ) that was contracted with either NE or KCl. Fura-3 (Ca)cyt signal caused by NO was small and transient in high K+-, but large and sustained in NE-contracted aorta. The inhibitory potency of STZ expressed in terms Of IC50 was 5.14 and 3.88 gM in NE and in high K+, respectively. These
results
suggest that modification of the cellular mobilization of Ca2+ rather than cGMP levels may be an important mechanism for the NO-mediated relaxation when vascular membrane is depolarized, such as atherosclerosis and hypertension.

Keyword

Nitric oxide; Ca2+ sensitivity; cGMP; Vascular smooth muscle; Depolarization

MeSH Terms

15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Animals
Aorta
Aorta, Thoracic
Atherosclerosis
Cytosol*
Guanylate Cyclase
Hypertension
Inhibitory Concentration 50
Membranes
Muscle, Smooth
Muscle, Smooth, Vascular*
Myosin-Light-Chain Kinase
Nitric Oxide
Potassium
Rats
Relaxation*
Streptozocin
15-Hydroxy-11 alpha,9 alpha-(epoxymethano)prosta-5,13-dienoic Acid
Guanylate Cyclase
Myosin-Light-Chain Kinase
Nitric Oxide
Potassium
Streptozocin