Question

1. What is antidiuretic hormone (ADH)? What effect does it have on blood volume and pressure, and what stimulates its secretion and what are its actions?
2. What effect would the change in MAP due to heart failure have on RAAS and ADH? How and why?
3. What effect would activation of angiotensin II and ADH have on blood flow to the heart and pressure in the heart chambers?
4. BNP is elevated in Mark’s blood. What effect does BNP have on blood volume and pressure and how does it achieve this?
5. Sacubitril is used to keep brain natriuretic peptide (BNP) levels in the blood elevated. What beneficial effect does sacubetril have on a person with left ventricle heart failure?

Answer 1

* ADH means anti diuretic hormone. It is also called vasopressin. It is a hormone secreted by hypothalamus in brain and stored in posterior pituitary gland. ADH helps in maintaining the regulation and balance the amount of water in blood.

* ADH helps to control blood pressure by acting on the kidneys and the blood vessels. Its most important role is to conserve the fluid volume of the body by reducing the amount of water passed out in the urine.

* Higher concentration of ADH causes blood vessels to constrict and this increases blood pressure ( arterial blood pressure). A deficiency of body fluid (dehydration) can only be finally restored by increasing water intake.

* Anti diuretic hormone increases water and urea permeability of the distal nephron, leading to excretion of a small volume of concentrated urine, thereby minimizing further loss of blood volume and decreasing the osmolarity of the plasma back toward normal.

* ADH is normally released by the pituitary in response to sensors that detect an increase in blood osmolality or decrease in blood volume. The kidneys respond to ADH by conserving water and producing urine that is more concentrated.

** Because of heart failure, the muscles of heart have low ability to pump, due to which MAP ( mean arterial pressure ) decreases and trigger activation of RAAS ( renin angiotensin system ) and release of ADH.

- In heart failure with a low cardiac output state, activation of the RAAS serves as a compensatory mechanism to maintain cardiac output. Reduced renal blood flow and sodium delivery to the distal tubule leads to renin release, which is exacerbated further by increased sympathetic tone. Renin cleaves angiotensinogen to form the inactive decapeptide angiotensin I. In turn, ACE cleaves angiotensin I to form the active angiotensin II.  While the majority of ACE in the body is found in the pulmonary vasculature, there is increasing evidence for local RAAS systems at the tissue level, especially in the heart, kidneys, and vasculature.

** Angiotensin increases blood pressure without decreasing heart rate because it resets the baroreflex control of heart rate to a higher pressure.
Because of ADH, urine formation is decreased and because of which there is increase in blood volume, arterial pressure and cardiac output.

** Brain natriuretic peptide decreases plasma volume and blood pressure in response to increased tension of respective cardiac chamber. The net effect of BNP is a decrease in blood pressure due to decrease in systemic vascular resistance and afterload.

The release of these peptides by the heart is stimulated by atrial and ventricular distension, as well as by neurohumoral stimuli, usually in response to heart failure. The main physiological actions of natriuretic peptides is to reduce arterial pressure by decreasing blood volume and systemic vascular resistance.

** Sacubitril helps to improve clinical outcomes in patients with heart failure and reduced ejection fraction, but its effects on left ventricular systolic function and reverse remodelling parameters. Sacubitril improves left ventricular ejection fraction and reverse cardiac remodelling