Compensatory responses

Activation of both the RAAS and the SNS also contribute to vasoconstriction in an attempt to redistribute blood flow from peripheral organs such as the kidneys to coronary and cerebral circulation.7 However, arterial vasoconstriction leads to impaired forward ejection of blood from the heart due to an increase in afterload. This results in a decrease in CO and continued stimulation of compensatory responses, creating a vicious cycle of neurohormonal activation. 

TABLE 3-2. Beneficial and Detrimental Effects of the Compensatory Responses in Heart Failure... 

Compensatory Response Beneficial Effects of Compensation Detrimental Effects of Compensation... 

Vasoconstriction Maintain blood pressure and perfusion in the face of reduced cardiac output Increased MV02 Increased afterload decreases stroke volume and further activates the compensatory responses... 

Vasodilators. Hydralazine causes direct relaxation of arteriolar smooth muscle. An important consequence of this vasodilation, however, is reflex tachycardia (T CO). It may also cause sodium retention (T plasma volume). The resulting increase in CO tends to offset effects of the vasodilator. Therefore, these drugs are most effective when administered along with sympathetic agents such as P-adrenergic receptor antagonists, which prevent unwanted compensatory responses by the heart. 

Prolonged 3 agonist treatment causes homologous desensitization in contrast to the heterologous nature of ft receptor desensitization. Furthermore, 3 agonists do not cause adaptive increases in adenylyl cyclase activity [74]. The lack of these compensatory responses may be one reason that 3 agonists do not cause addiction [99]. 

There are four primary types of acid-base disturbances, which can occur independently or together as a compensatory response. 

Estimate compensatory response (see Table 55-7 in Pharmacotherapy A Pathophysiologic Approach, seventh edition). 

The earliest compensatory response is to chemically buffer excess bicarbonate by releasing hydrogen ions from intracellular proteins, phosphates, and hemoglobin. If respiratory alkalosis is prolonged (more than 6 hours), the kidneys attempt to further compensate by increasing bicarbonate elimination. 

The early compensatory response to acute respiratory acidosis is chemical buffering. If respiratory acidosis is prolonged (more than 12 to 24 hours), renal excretion of H+ increases, which generates new bicarbonate. 

Change in site of action e.g., increased synthesis of dihydrofolate reductase may occur as a compensatory response to methotrexate. 

The value of diuretics lies in their ability to reverse the Na retention commonly associated with many antihypertensive drugs that probably induce Na retention and fluid volume expansion as a compensatory response to blood pressure reduction. 

Chapter 12 contains additional discussion of vasodilators. All the vasodilators that are useful in hypertension relax smooth muscle of arterioles, thereby decreasing systemic vascular resistance. Sodium nitroprusside and the nitrates also relax veins. Decreased arterial resistance and decreased mean arterial blood pressure elicit compensatory responses, mediated by baroreceptors and the sympathetic nervous system (Figure 11-4), as well as renin, angiotensin, and aldosterone. Because sympathetic reflexes are intact, vasodilator therapy does not cause orthostatic hypotension or sexual dysfunction. 

Compensatory responses to vasodilators basis for combination therapy with 13 blockers and diuretics. Effect blocked by diuretics. Effect blocked by 13 blockers. 

The indirect effects of nitroglycerin consist of those compensatory responses evoked by baroreceptors and hormonal mechanisms responding to decreased arterial pressure (see Figure 6-7) this often results in tachycardia and increased cardiac contractility. Retention of salt and water may also be significant, especially with intermediate- and long-acting nitrates. These compensatory responses contribute to the development of tolerance. 

Neurohumoral (extrinsic) compensation involves two major mechanisms (previously presented in Figure 6-7)—the sympathetic nervous system and the renin-angiotensin-aldosterone hormonal response—plus several others. Some of the pathologic as well as beneficial features of these compensatory responses are illustrated in Figure 13-2. The baroreceptor reflex appears to be reset, with a lower sensitivity to arterial pressure, in patients with heart failure. As a result, baroreceptor sensory input to the vasomotor center is reduced even at normal pressures sympathetic outflow is increased, and parasympathetic outflow is decreased. Increased sympathetic outflow causes tachycardia, increased cardiac contractility, and increased vascular tone. Vascular tone is further increased by angiotensin II and endothelin, a potent vasoconstrictor released by vascular endothelial cells. The result is a vicious cycle that is characteristic of heart failure (Figure 13-3). Vasoconstriction increases afterload, which further reduces ejection fraction and cardiac output. Neurohumoral antagonists and vasodilators... 

Some compensatory responses that occur during congestive heart failure. In addition to the effects shown, sympathetic discharge facilitates renin release, and angiotensin II increases norepinephrine release by sympathetic nerve endings (dashed arrows). 

Down-regulation A prolonged decrease in the number and/or sensitivity of drug receptors, usually occurring as a compensatory response to overstimulation of the receptor. 

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