Title

A study of the calcium regulatory mechanisms involved in maintained agonist-induced vascular smooth muscle tone

Date of Award

1989

Availability

Article

Degree Name

Doctor of Philosophy (Ph.D.)

Department

Pharmacology

First Committee Member

Cornelis van Breemen, Committee Chair

Abstract

Isometric tension was measured in parallel with $\sp{45}$Ca influx in rabbit aorta or simultaneously with (Ca$\sp{2+}$) $\sb{\rm i}$ in rabbit inferior vena cava loaded with fura-2. In the presence of external Ca$\sp{2+}$, phenylephrine, norepinephrine and high K$\sp+$ caused a maintained increase in tension, $\sp{45}$Ca influx and (Ca$\sp{2+}$) $\sb{\rm i}$ which were markedly inhibited in the absence of extracellular Ca$\sp{2+}$. In (Ca$\sp{2+}$) $\sb{\rm i}$ vs force curves, the norepinephrine curve was shifted to the left of that of high K$\sp+$. The protein kinase C activator TPA induced a slow increase in tension and shifted the (K$\sp+$) $\sb{\rm e}$-force relationship to the left without any change in (Ca$\sp{2+}$) $\sb{\rm i}$. TPA alone did not maintain the contraction initiated by high K$\sp+$. The protein kinase C inhibitor H-7 completely inhibited the contraction induced by TPA but only partially inhibited the phenylephrine-, norepinephrine- and high K$\sp+$-induced contraction without changing $\sp{45}$Ca influx or (Ca$\sp{2+}$) $\sb{\rm i}$. In the presence of external Ca$\sp{2+}$, ryanodine caused a maintained increase in (Ca$\sp{2+}$) $\sb{\rm i}$ which was not inhibited by diltiazem, but completely abolished by La$\sp{3+}$ or in Ca$\sp{2+}$-free solution. Ryanodine caused a small increase in tension and transient decrease in the caffeine-releasable Ca$\sp{2+}$. Ryanodine did not enhance the high K$\sp+$-induced force, $\sp{45}$Ca influx and (Ca$\sp{2+}$) $\sb{\rm i}$. It is concluded that the maintained agonist-induced vascular tone is due to (1) Ca$\sp{2+}$ influx from the extracellular space, (2) increased myofilament force sensitivity probably due to activation of protein kinase C, and (3) inhibition of Ca$\sp{2+}$ buffering by the sarcoplasmic reticulum.

Keywords

Health Sciences, Pharmacology

Link to Full Text

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