Renin release

By themselves, potassium-sparing agents are relatively weak antihypertensives. In general, there are four ways to reduce the activity of the RAS. The first way is the use of p-blockers to reduce renin release from the juxtaglomerular (JG). The second way, the direct inhibition of the activity of renin, although being actively investigated has not been successful in the clinical arena thus far. The third way is to inhibit the activity of the... 

Matsumura, Y., Miyawaki, N., Sasaki, Y. and Morimoto, S. (1985). Inhibitory effects of norepinephrine, methoxamine and phenylephrine on renin release from rat kidney cortical slices. J. Pharmacol. Exp. Ther. 233, 782-787. 

There is a paucity of clinical trial evidence comparing the benefit of diuretics to other therapies for symptom relief or long-term outcomes. Additionally, excessive preload reduction can lead to a decrease in CO resulting in reflex increase in sympathetic activation, renin release, and the expected consequences of vasoconstriction, tachycardia, and increased myocardial oxygen demand. Careful use of diuretics is recommended to avoid overdiuresis. Monitor serum electrolytes such as potassium, sodium, and magnesium frequently to identify and correct imbalances. Monitor serum creatinine and blood urea nitrogen daily at a minimum to assess volume depletion and renal function. 

Theophylline and caffeine enhance renin release from the kidneys. 

Lead may affect renin release from the kidney by affecting calcium ion fluxes in the juxtaglomerular cells, as discussed previously under Cardiovascular Effects. 

Sympathetic nerve activity causes an increase in blood pressure through many mechanisms, including an increase in cardiac activity and vasoconstriction. Activation of the sympathetic system also causes the stimulation of Pi-adrenergic receptors on the renin-producing cells, which promotes renin release. 

Formation of angiotensin II requires the release of renin from the granular cells. Therefore, the factors affecting renin release must be considered ... 

The exact hypotensive mechanism of /1-blockers is not known but may involve decreased cardiac output through negative chronotropic and inotropic effects on the heart and inhibition of renin release from the kidney. 

Hydralazine and minoxidil cause direct arteriolar smooth muscle relaxation. Compensatory activation of baroreceptor reflexes results in increased sympathetic outflow from the vasomotor center, producing an increase in heart rate, cardiac output, and renin release. Consequently, the hypotensive effectiveness of direct vasodilators diminishes over time unless the patient is also taking a sympathetic inhibitor and a diuretic. 

Minoxidil is a more potent vasodilator than hydralazine, and the compensatory increases in heart rate, cardiac output, renin release, and sodium retention are more dramatic. Severe sodium and water retention may precipitate congestive heart failure. Minoxidil also causes reversible hyper-... 

The relevance of either the experimentally demonstrated central hypotensive action of the 3-blockers, or their ability to antagonise sympathetically mediated renin release remains to be proven. While it is still possible that the mechanism of the anti-hypertensive action of the 3-blocking drugs could contain both a central and a renin-inhibitary component, the clinical evidence would appear to rule against the possibility of either being a major component of the mode-of-action. 

Both in the experimental animal and in patients, administration of clonidine suppresses renin release by the kidney(32) (Figure 8). These observations suggest the possibility that this... 

Surgery/Anesthesia In patients undergoing major surgery or during anesthesia with agents that produce hypotension, ACEIs will block angiotensin II formation secondary to compensatory renin release. 

While the rate limiting step of the cascade is the renin release, the biological active component is the octapeptide angiotensin n. It is an essential regulator of fluid and electrolyte balance as well as blood pressure. It exerts its actions on various structures like blood vessels, adrenal cortex, kidney and central nervous system. Although at least two different receptor subtypes for angiotensin II have been identified (ATi and AT2) the ATi-subtype is responsible for most of the cardiovascular effects of the agonist. 

Phenoxybenzamine and phentolamine, in addition to blocking postsynaptic a-receptors, also block aj-receptors on nerves and therefore can enhance the release of norepinephrine. When norepinephrine exerts a postsynaptic action by means of -adrenoceptors (e.g., cardiac stimulation, renin release), blockade of presy-naptic a2-receptors by phenoxybenzamine and phentolamine may actually potentiate the responses. Prazosin blocks responses mediated by postsynaptic aj-receptors but has no effect on the presynaptic a2-receptors. Thus,... 

The actions of p-blockers on blood pressure are complex. After acute administration, blood pressure is only slightly altered. This is because of the compensatory reflex increase in peripheral vascular resistance that results from a (3-blocker-induced decrease in cardiac output. Vasoconstriction is mediated by a-receptors, and a-receptors are not antagonized by (3-receptor blocking agents. Chronic administration of (3-blockers, however, results in a reduction of blood pressure, and this is the reason for their use in primary hypertension (see Chapter 20). The mechanism of this effect is not well understood, but it may include such actions as a reduction in renin release, antagonism of (3-receptors in the central nervous system, or antagonism of presynaptic facilita-tory (3-receptors on sympathetic nerves. 

B. The adrenoceptors that epinephrine acts on to affect heart rate, renin release, bronchiolar tone, and glycogenolysis are (3-receptors. Prazosin is an a-antagonist so would not antagonize epinephrine at those receptors. The radial smooth muscle in the iris has a-receptors that when activated, contract the radial muscle which dilates the pupil. This action is antagonized by prazosin. 

Increased pressure in afferent arteriole leads to decreased renin release by JG cells. 

Phenoxybenzamine and phentolamine have been available for a number of years and are sometimes referred to as classical a-blockers. The frequency of their use for the treatment of primary hypertension has greatly diminished in recent years because of the development of drugs such as prazosin that are relatively selective for tti-receptors. ai-Receptor-selective antagonists will not potentiate the release of norepinephrine from sympathetic nerves. Thus, the stimulation of the heart and renin release, actions that limit the usefulness of classical a-blockers, are less with aj-selective antagonists. 

The mechanism by which 3-blockers produce a sustained reduction in blood pressure in patients with primary hypertension is not completely understood, but it may include such actions as reduction in renin release, antagonism of central nervous system (CNS) P-receptors, or antagonism of presynaptic facilitatory P-receptors on sympathetic nerves. 

Which of the following antihypertensive agents would decrease renin release ... 

Alpha receptors There are two major groups of alpha receptors, and a. Activation of postsynaptic receptors increases the intracellular concentration of calcium by activation of a phospholipase G in the cell membrane via G protein, receptor is responsible for inhibition of renin release from the kidney and for central a-adrenergically mediated blood pressure depression. 

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