Nitric oxide and CaMKII: Critical steps in the cardiac contractile response To IGF-1 and swim training

The effect of short-term exposure to homocysteine (Hcy) on the contractile characteristics of rat aortic tissue was assessed both in vitro and in vivo. The contractile response of Hcy-treated aortic rings in culture for 1 or 4 days was unchanged from control responses. By comparison, aortic rings from animals injected with Hcy showed marked attenuation of response compared with controls injected with saline, cysteine or methionine. The contractile response to K+ was decreased within 24 hours of Hcy injection, whereas the response to both K+ (-27%) and noradrenaline (-56%) was significantly decreased by 4 days. In contrast, the contractile response to phorbol-12,13-dibutyrate was not different between Hcy and control groups. Intimal rubbing completely restored the responsiveness of Hcy-treated tissue to K+ and noradrenaline. By comparison, L-NAME only partially restored contractile responsiveness, while the cyclooxygenase inhibitor indomethacin had no effect on contractile attenuation induced by Hcy. Western blot analysis showed a 2-fold increase of endothelial nitric oxide synthase (eNOS) and a 3-fold increase in inducible nitric oxide synthase (iNOS) protein expression in the aortic endothelial cells from Hcy-injected rats. The results indicate an early detectable effect of Hcy on the in vivo contractile properties of vascular smooth muscle. The effect is endothelium-mediated and may vary depending on the agonist studied. The mechanism is uncertain but appears to involve increased nitric oxide (NO) production. Finally, the data suggest that attenuation of contraction may not be due to a direct effect of Hcy but that the compound is modified or acts indirectly in vivo.Key words: nitric oxide, nitric oxide synthase, in vivo, smooth muscle.

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Renal vasoconstriction by vasopressin V1a receptors is modulated by nitric oxide, prostanoids, and superoxide but not the ADP ribosyl cyclase CD38

AJP Renal Physiology ◽

10.1152/ajprenal.00664.2013 ◽

2014 ◽

Vol 306 (10) ◽

pp. F1143-F1154 ◽

Cited By ~ 8

Author(s):

Nicholas G. Moss ◽

Tayler E. Kopple ◽

William J. Arendshorst

Keyword(s):

Nitric Oxide ◽

Contractile Response ◽

Receptor Activation ◽

Wild Type ◽

Renal Vasoconstriction ◽

Adp Ribosyl Cyclase ◽

Cyclic Adp Ribose ◽

Renal Vascular ◽

Dose Dependent

Renal blood flow (RBF) responses to arginine vasopressin (AVP) were tested in anesthetized wild-type (WT) and CD38−/− mice that lack the major calcium-mobilizing second messenger cyclic ADP ribose. AVP (3–25 ng) injected intravenously produced dose-dependent decreases in RBF, reaching a maximum of 25 ± 2% below basal RBF in WT and 27 ± 2% in CD38−/− mice with 25 ng of AVP. Renal vascular resistance (RVR) increased 75 ± 6% and 78 ± 6% in WT and CD38−/− mice. Inhibition of nitric oxide (NO) synthase with nitro-l-arginine methyl ester (l-NAME) increased the maximum RVR response to AVP to 308 ± 76% in WT and 388 ± 81% in CD38−/− ( P < 0.001 for both). Cyclooxygenase inhibition with indomethacin increased the maximum RVR response to 125 ± 15% in WT and 120 ± 14% in CD38−/− mice ( P < 0.001, <0.05). Superoxide suppression with tempol inhibited the maximum RVR response to AVP by 38% in both strains ( P < 0.005) but was ineffective when administered after l-NAME. The rate of RBF recovery (relaxation) after AVP was slowed by l-NAME and indomethacin ( P < 0.001, <0.005) but was unchanged by tempol. All vascular responses to AVP were abolished by an AVP V1a receptor antagonist. A V2 receptor agonist or antagonist had no effect on AVP-induced renal vasoconstriction. Taken together, the results indicate that renal vasoconstriction by AVP in the mouse is strongly buffered by vasodilatory actions of NO and prostanoids. The vasoconstriction depends on V1a receptor activation without involvement of CD38 or concomitant vasodilatation by V2 receptors. The role of superoxide is to enhance the contractile response to AVP, most likely by reducing the availability of NO rather than directly stimulating intracellular contraction signaling pathways.

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