A 44-year-old previously healthy woman comes to the emergency department due to a 2-day history of left flank pain, dysuria, fever, and chills. Temperature is 38.9 C (102 F) , blood pressure is 80/40 mm Hg, and pulse is 140/min and regular. Physical examination shows left costovertebral angle tenderness. Laboratory studies reveal leukocytosis, pyuria, and bacteriuria. Empiric broad-spectrum antibiotics and intravenous fluids are administered. The patient remains persistently hypotensive, and an intravenous phenylephrine infusion is begun. Several minutes later, her heart rate decreases to 100/min. Compared to just prior to the infusion, which of the following intracellular changes are expected in this patient?

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11ec160b_3ca4_d7aa_9249_038649e9a8c4_MD0001_00 Phenylephrine is a selective alpha-1 adrenergic receptor agonist that causes vasoconstriction and increased blood pressure by increasing inositol triphosphate (IP₃) levels in vascular smooth muscle cells. The abrupt increase in blood pressure triggers a baroreceptor reflex, resulting in increased parasympathetic and decreased sympathetic outflow to the heart and vasculature. The baroreceptor reflex-driven changes in the heart are mediated by beta-1 adrenergic receptors and muscarinic-2 receptors. Both reduced sympathetic stimulation of beta-1 receptors and increased parasympathetic stimulation of muscarinic-2 receptors trigger a decrease in cyclic AMP (cAMP) levels, which leads to a decrease in heart rate and contractility to reduce cardiac output and lessen the increase in blood pressure. The reduction in heart rate is driven in part by decreased inward calcium current during phases 4 and 0 of the sinoatrial node action potential. The above baroreceptor response also affects vascular smooth muscle, which is mostly under sympathetic control. Although this response causes reduced sympathetic stimulation of vascular alpha-1 receptors, the infusion of phenylephrine still maintains IP₃ activity above baseline, resulting in a persistent vasoconstrictive effect. In contrast, an abrupt decrease in blood pressure triggers the opposite regulatory response via the baroreceptor reflex. Educational objective: Phenylephrine increases blood pressure via an alpha-1 receptor-mediated increase in inositol triphosphate in vascular smooth muscle cells. The abrupt increase in blood pressure triggers a reflexive increase in parasympathetic activity while decreasing sympathetic outflow. This leads to decreased cyclic AMP activity in the heart (mediated by beta-1 adrenergic and muscarinic-2 receptors), which decreases heart rate and myocardial contractility. The reduction in heart rate is driven in part by decreased inward calcium current in sinoatrial cells.

A 44-Year-Old Previously Healthy Woman Comes to the Emergency Department