Stimulation of Aldosterone Release

Peak B is closely related to a-MSH it has an identical amino acid composition and electron impact mass spectrum (AT-acetyl-Ar,0,S-permethyl derivative) and is converted into a-MSH on base hydrolysis (Fig. 9). Using the nascent mass spectrometric technique of fast atom bombardment (FAB) (Barber et al, 1981 Morris et al., 1981), the molecular weight of peak B was shown to be 42 mass units higher than a-MSH. These data together with EIMS analysis of underivatized peptides obtained by proteolytic digestion of peak B, allowed us to determine its structure as bis acetyl (Ser 1) a-MSH. 

The structure of peak C is presently under investigation. Our preliminary mass spectrometric studies have shown that a peptide arising from 

It was reported (Matsuoka et a/., 1980) that P-Lipotropin (P-LPH) had similar glomerulosa-stimulating activity. On fractionating a sample p-LPH, from the same source, the major region of activity was coincident with the elution position of ACTH 1-39 and was well separated from inactive P-LPH (Fig. 10) (Vinson et al., 1981). This again clearly demonstrates the importance of characterizing presumed pure samples prior to their use as biological standards. 

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The 5-HT4 receptors modulate the activities of channels and transporters by increasing cAMP levels. These include activation of L-type Ca2+ channels (326), chloride currents in human jejunal mucosa and rat distal colon (330,331), and the If pacemaker current in atrial myocytes (332) and stimulation of aldosterone release from the adrenal glands (333,334), striatal dopamine release (324), hippocampal and frontal cortex acetylcholine release (335,336), and hippocampal 5-HT release (337). 5-HT4 receptors also inhibit various channels, including a KV3.2-like delayed rectifier K+ channel (303), a voltage-activated K+ channel in colliculi neurons (320,338), a Ca2+-activated, afterhyperpolariz-ing, and K+ current in hippocampus (325). 

These drugs reduce aldosterone levels (angiotensin II is a major stimulant of aldosterone release) and cause potassium retention. Potassium accumulation may be marked, especially if the patient has renal impairment, is consuming a high potassium diet, or is taking other drugs that tend to conserve potassium, eg, potassium sparing diuretics. Under these circumstances, potassium concentrations may reach toxic levels. 

B. Effects Angiotensin II is a potent arteriolar vasoconstrictor and stimulant of aldosterone release. All directly incTeases peripheral vascular resistance and, through aldosterone, causes renal sodium retention. All also facilitates the release of norepinephrine from adrenergic nerve endings via presynaptic heteroreceptor action. All of these effects are mediated by the angiotensin AT, receptor, a G, -coupled receptor. 

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. 

The rate of aldosterone secretion is subject to several influences. ACTH produces a moderate stimulation of its release, but this effect is not sustained for more than a few days in the normal individual. Although aldosterone is no less than one third as effective as cortisol in suppressing ACTH, the quantities of aldosterone produced by the adrenal cortex and its plasma concentrations are insufficient to participate in any significant feedback control of ACTH secretion. 

Circulating angiotensin II can elevate BP through pressor and volume effects. The pressor effects include direct vasoconstriction, stimulation of catecholamine release from the adrenal meduUa, and centrally mediated increases in sympathetic nervous system activity. Angiotensin II also stimulates aldosterone synthesis from the adrenal cortex. This leads to sodium and water reabsorption that increases plasma volume, total peripheral resistance, and ultimately, BP. Clearly, any disturbance in the body that leads to activation of the RAAS could explain chronic hypertension. 

Release of Aldosterone from the Adrenal Cortex Angll stimulates the zona glomerulosa of the adrenal cortex to increase the synthesis and secretion of aldosterone and also exerts permissive effects that augment responses to ACTH and K+. Increased output of aldosterone is elicited by concentrations of Angll that have little or no acute effect on blood pressure. Aldosterone acts on the distal and collecting tubules to cause retention of Na+ and excretion of K+ and H+. Angll-induced stimulation of aldosterone synthesis is enhanced by hyponatremia or hyperkalemia. 

Adrenal Inhibition of angiotensin II stimulated aldosterone release... 

Hyperkalemia results from reduced angiotensin II-stimulated aldosterone release. The risk of hyperkalemia with ACE... 

A nontrophic hormone acts on nonendocrine target tissues. For example, parathormone released from the parathyroid glands acts on bone tissue to stimulate the release of calcium into the blood. Aldosterone released from the cortical region of the adrenal glands acts on the kidney to stimulate the reabsorption of sodium into the blood. 

The mechanism by which potassium regulates aldosterone secretion is unclear however, this ion appears to have a direct effect on the adrenal cortex. An increase in the level of potassium in the blood stimulates the release of aldosterone. The effect of aldosterone on the kidney then decreases the level of potassium back to normal. 

A decrease in blood volume or blood pressure may result in a decrease in the blood flow to the kidney. The kidney monitors renal blood flow by way of stretch receptors in the vessel walls. A decrease in renal blood flow stimulates the release of renin. The subsequent secretion of aldosterone causes retention of sodium and water and, therefore, an increase in blood volume and blood pressure back to normal. An increase in renal blood flow tends to cause the opposite effect. 

HT4 receptors are also present in the pig and human hearts, primarily located in the atrium [9]. Experiments showed that stimulation of these receptors can result in tachycardia and can trigger positive inotropic effects. Moreover, it has been demonstrated that the 5-HT4 receptor is present in the human detrusor muscle and facilitates a cholinergic mechanism which may lead to increased bladder contractions [10]. Finally, acute (but not repeated) stimulation of 5-HT4 receptors present on the human adrenal cortex has been reported to trigger the release of corticosterone and aldosterone [11]. 

A. Angiotensin II has diverse physiological effects, including stimulating the synthesis and release of aldosterone from the adrenal cortex. This effect of angiotensin II results in fluid and water retention. The other answers are incorrect in that angiotensin II... 

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