Physiologists conduct a series of experiments on hypophysectomized animals to investigate the effects of cortisol on vascular reactivity. Their initial tests show that administration of cortisol alone does not elicit a vascular response. Next, the researchers measure vascular reactivity to an infusion of norepinephrine both with and without pretreatment with cortisol. The results of their experiments are shown in the graph below. Which of the following pharmacologic principles best describes the effect of cortisol in this experiment?

Question

Physiologists conduct a series of experiments on hypophysectomized animals to investigate the effects of cortisol on vascular reactivity.  Their initial tests show that administration of cortisol alone does not elicit a vascular response.  Next, the researchers measure vascular reactivity to an infusion of norepinephrine both with and without pretreatment with cortisol.  The results of their experiments are shown in the graph below.  Which of the following pharmacologic principles best describes the effect of cortisol in this experiment?

Quizplus · Accepted Answer

Although cortisol has no direct vasoactive properties, it augments the vasoconstrictive effects of catecholamines and angiotensin II. The above graph shows that the administration of norepinephrine produced a limited degree of vasoconstriction that was markedly increased following pretreatment with cortisol. This phenomenon is termed permissiveness; it occurs when a hormone has no direct effect on a physiologic process but allows another hormone to exert its maximal effect on that process. Cortisol exerts its potentiating effect on vasoconstriction in part through upregulation of alpha-1 adrenergic receptors on vascular smooth muscle cells. In adrenal insufficiency, low cortisol levels can contribute to hypotensive crisis by decreasing vascular responsiveness to norepinephrine and angiotensin II. Cortisol also has a permissive effect on catecholamine-mediated bronchodilation and glucagon-mediated release of glucose from the liver. (Choices A and D) The combination of 2 drugs with similar actions can have a synergistic or additive effect. When the combined effect of 2 drugs is equal to the sum of their individual effects, it is termed an additive response (eg, 1 + 1 = 2). When the combined effect exceeds the sum of the individual drugs' effects, the interaction is called synergistic (eg, 1 + 1 > 2). In this case, cortisol's influence on vascular responsiveness is best described as permissive rather than synergistic because cortisol has no intrinsic vasoconstrictive effect (eg, 1 + 0 > 1). (Choice B) Alterations in metabolism can change a drug's pharmacokinetic and pharmacodynamic properties. For example, certain drugs (eg, amiodarone, fluconazole) can inhibit the P450 cytochrome oxidase system, decreasing the metabolism of other drugs metabolized through this pathway, which can lead to additive or synergistic responses. (Choice E) Tachyphylaxis describes decreased drug responsiveness in a short period following one or more doses (ie, rapidly developing tolerance). Time is not quantified in the graph; therefore, drug response over time cannot be assessed. Educational objective: A permissive hormone has no effect on a physiologic process by itself but allows another hormone to exert its maximal effect on that process. Cortisol exerts a permissive effect on catecholamines to potentiate vasoconstriction and bronchodilation; it also has a permissive effect on glucagon to increase glucose release from the liver. __________ References: Glucocorticoids and vascular reactivity. (http://www.ncbi.nlm.nih.gov/pubmed/15320828)

Physiologists Conduct a Series of Experiments on Hypophysectomized Animals to Investigate