Renal vascular receptor

The renal vascular receptor functions as a stretch receptor, with decreased stretch leading to increased renin release and vice versa. The receptor is apparently located in the afferent arteriole, possibly in the juxtaglomerular cells. Stretch-induced changes in renin release are mediated by changes in Ca2+ concentration in the juxtaglomerular cells. 

The rate at which renin is secreted by the kidney is the primary determinant of activity of the renin-angiotensin system. Renin secretion is controlled by a variety of factors, including a renal vascular receptor, the macula densa, the sympathetic nervous system, and angiotensin II. 

Vasopressin causes vasoconstrictive effects that, unlike adrenergic receptor agonists, are preserved during hypoxia and severe acidosis. It also causes vasodilation in the pulmonary, coronary, and selected renal vascular beds that may reduce pulmonary artery pressure and preserve cardiac and renal function. However, based on available evidence, vasopressin is not recommended as a replacement for norepinephrine or dopamine in patients with septic shock but may be considered in patients who are refractory to catecholamine vasopressors despite adequate fluid resuscitation. If used, the dose should not exceed 0.01 to 0.04 units/min. 

Pharmacology Initially, clonidine stimulates peripheral -adrenergic receptors producing transient vasoconstriction. Stimulation of alpha-adrenergic in the brain stem results in reduced sympathetic outflow from the CNS and a decrease in peripheral resistance, renal vascular resistance, heart rate, and blood pressure. Pharmacokinetics Blood pressure declines within 30 to 60 minutes after an oral... 

Intravenous administration of dopamine promotes vasodilation of renal, splanchnic, coronary, cerebral, and perhaps other resistance vessels, via activation of Di receptors. Activation of the Di receptors in the renal vasculature may also induce natriuresis. The renal effects of dopamine have been used clinically to improve perfusion to the kidney in situations of oliguria (abnormally low urinary output). The activation of presynaptic D2 receptors suppresses norepinephrine release, but it is unclear if this contributes to cardiovascular effects of dopamine. In addition, dopamine activates Bj receptors in the heart. At low doses, peripheral resistance may decrease. At higher rates of infusion, dopamine activates vascular a. receptors, leading to vasoconstriction, including in the renal vascular bed. Consequently, high rates of infusion of dopamine may mimic the actions of epinephrine. 

Another topographical model, advanced for the renal vascular DA receptor by Erhardt (92) is described in greater detail in another section of this monograph (93). This model locates important receptor sites on Cartesian coordinates. It extends the McDermed model by suggesting a second site of steric hindrance about 2.0 A above the plane of the ethylamine chain and an auxiliary binding site, alluded to previously, opposite the principal site of bulk intolerance. As this model, which is consistent with the structures of most DA receptor agonists, specifically locates the amine and "meta"-0H it can be utilized to rationalize the enantioselectivity of known chiral DA receptor agonists (94). 

A topographical model has been proposed to explain why (E)-2-(3,4-dihydroxyphenyl)cyclopropylamine, 1, and alpha-methyldopamine (AMDA) are inactive in the renal vascular dopamine (DA) receptor system. In this model a steric protrusion (S2) resides approximately lX above the generalized plane of the receptor and acts to impede interaction with molecules such as 1 and AMDA which possess additional bulk in this region. Recent developments in DA structure-activity relationships offer further support for the existence of the S2 site. 

Figure 1. Topographical model of the renal vascular dopamine receptor (12).

Similarly, renal function is markedly affected by the renovascular actions of endothelin [47]. However, the presence of non-vascular endothelin receptor sites in the kidney suggests that endothelin may modulate renal function by a direct action [48]. Indeed, a direct contractile and mitogenic action of ET-1 on mesangial cells has been demonstrated [49]. The different isoforms show different profiles in the kidney. ET-1 increases renal vascular resistance and glomerular filtration rate [50]. ET-3, however, decreases renal flow and GFR at low doses, although higher doses produce effects similar to those seen with ET-1 [51]. 

Angiotensin type lAand IB receptor double knockout (ATI DKO) mice Loss of angiotensin ii-induced contraction, reduced vasoconstriction to norepinephrine and endothelial cell dysfunction contribute to the renal vascular phenotype of ATI DKO mice [227]... 

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