Aldosterone vasoconstriction

Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and C-type natriuretic peptide (CNP) are members of a family of so-called natriuretic peptides, synthesized predominantly in the cardiac atrium, ventricle, and vascular endothelial cells, respectively (G13, Y2). ANP is a 28-amino-acid polypeptide hormone released into the circulation in response to atrial stretch (L3). ANP acts (Fig. 8) on the kidney to increase sodium excretion and glomerular filtration rate (GFR), to antagonize renal vasoconstriction, and to inhibit renin secretion (Ml). In the cardiovascular system, ANP antagonizes vasoconstriction and shifts fluid from the intravascular to the interstitial compartment (G14). In the adrenal cortex, ANP is a powerful inhibitor of aldosterone synthesis (E6, N3). At the hypothalamic level, ANP inhibits vasopressin secretion (S3). It has been shown that some of the effects of ANP are mediated via a newly discovered hormone, called adreno-medullin, controlling fluid and electrolyte homeostasis (S8). The diuretic and blood pressure-lowering effect of ANP may be partially due to adrenomedullin (V5). 

Widespread vasoconstriction supplements the increase in TPR induced by the sympathetic nervous system. Angiotensin II also causes vasoconstriction of the afferent arteriole in particular, which enhances the decrease in RBF and sodium filtration. Finally, angiotensin II promotes secretion of aldosterone from the adrenal cortex. Aldosterone then acts on the distal tubule and collecting duct to increase sodium reabsorption. 

Therefore, inhibition of ANP release leads to vasoconstriction and increased MAP. Furthermore, less ANP promotes the release of renin and secretion of aldosterone, which further enhance sodium reabsorption. 

ACE inhibitors (Table 8-2) decrease angiotensin II and aldosterone, attenuating many of their deleterious effects, including reducing ventricular remodeling, myocardial fibrosis, myocyte apoptosis, cardiac hypertrophy, norepinephrine release, vasoconstriction, and sodium and water retention. 

Endothelin eta Human cDNA Acute pancreatitis, artherosderosis, cancer, hypertension, congestive heart failure, diabetes, obesity, inflammation, myocardial ischemia, prostatic hypertrophy, pulmonary fibrosis, stroke, ulcer, pain Vasoconstriction, bronchoconstriction, positive cardiac inotropy, proliferative responses, aldosterone secretion, neuroprotection... 

Figure 22.15 How angiotensin-II increases blood pressure. Angiotensin-II causes vasoconstriction of smooth muscle in arterioles in addition, it stimulates synthesis and hence secretion of aldosterone from the adrenal cortex. Both of these effects increase blood pressure.

Angiotensin 11 can raise blood pressure in different ways, including (1) vasoconstriction in both the arterial and venous limbs of the circulation (2) stimulation of aldosterone secretion, leading to increased renal reabsorption of NaCl and water, hence an increased blood volume (3) a central increase in sympathotonus and, peripherally, enhancement of the release and effects of norepinephrine. 

Captopril, many others Inhibit angiotensin converting enzyme Reduce angiotensin II levels reduce vasoconstriction and aldosterone secretion increase bradykinin Hypertension heart failure, diabetes Oral Toxicity Cough, angioedema teratogenic... 

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... 

Figure 33-3. Summary of the renin-angiotensin-aldosterone system. Aldosterone secretion is controlled by several factors, including increased K+,ACTH, or angiotensin II.A1-dosterone acts to increase Na+ retention by both the kidney and colon.Aldosterone also promotes renal K+ excretion, which contributes to maintenance of Na+/K+ balance. In the absence of aldosterone, Na+ is lost, K+ is enhanced, the extracellular fluid volume is reduced, and mean arterial pressure and renal perfusion pressure are decreased. As a result, renin secretion is increased, leading to increased formation of angiotensin II, which promotes vasoconstriction and aldosterone secretion.

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