Vasodilating Agents

Vasodilating Agents

Shreyajit R. Kumar (Weill Cornell Medical College, USA), Andrew Sosa (Weill Cornell Medical College, USA) and Ilan Margulis (Weill Cornell Medical College, USA)
Copyright: © 2015 |Pages: 23
DOI: 10.4018/978-1-4666-8603-8.ch013
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This chapter discusses the salient features of arterial and venous dilating agents commonplace in the management of the post-cardiotomy surgical patient. A keen understanding of the underlying cellular mechanism, pharmacology, indication, safety profile, and controversies of clinical utility of vasodilating agents is imperative for routine use. The evidenced-based examination of each therapeutic modality will strengthen the practitioner's fund of knowledge for management of each pathophysiological state.
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Molecular Mechanisms: Smooth Muscle

Vascular smooth muscle constriction is dependent upon the translation of the synaptic action potential to muscle tension. Excitation-coupling describes the rise of intracellular calcium following receptor interaction with a neurotransmitter. Intracellular calcium rises trifold (see figure 1): (i) direct influx through voltage-gated calcium channels, (ii) g-protein ligand gated calcium channels, and (iii) IP3-phospholipase system. The latter, GTP binding protein – G Protein – is activated, and couples with phospholipase C to upregulate IP3 (inositol 1,4,5-triphosphate) production (Costanzo, 2014). The net effect is increased intracellular Calcium, liberated from the sarcoplasmic reticulum. Intracellular calcium-calmodulin complexes activate myosin cross-bridges, resulting in vasoconstriction. Increased systemic vascular resistance leads to a higher afterload and mean arterial pressure, and a parasympathetic bradycardic reflex. Alpha-receptor antagonism (e.g. phentolamine) perturbs intracellular calcium release, lowering overall systemic vascular resistance in a vasodilated state.

Figure 1.

Trifold mechanism that increases intracellular smooth muscle calcium

This figure was published in Physiology, Fifth Edition. Costanzo, Linda. Figure 1-30 Mechanisms for increasing intracellular [Ca2+] in smooth muscle. Copyright Elsevier 2014.

Molecular Mechanisms: Myocardial Contractility And Automaticity

Myocardial contractility is intimately dependent upon the excitation-coupling of cardiac action potential with intracellular calcium accumulation. Action potentials in the atrium, ventricular purkinje fibers, and sinoatrial nodes (Costanzo, 2014, see figure 2) involve four distinct phases of ion exchange (see table 1). Initial inward sodium flow results in rapid ventricular depolarization to +20mV. Long acting (L-type) calcium channels modulate a plateau phase and increased contractility. Myocardial tension is directly proportional to intracellular calcium concentrations. Repolarization to resting membrane potential is governed by potassium counterflow. Phase configuration varies in sinoatrial pacemaker cells, where a plateau – phase 2 – is absent, and the depolarization – phase 4 – dominates; this is the chief determinant of automaticity and heart rate.

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