Alpha-Adrenoceptors in the Developing Kidney

Abstract

Summary MATERIALS AND METHODSThe maturation of renal alpha-adrenoceptors was investigated in dogs. Alpha-adrenoceptors were characterized by radioligand binding using the alpha-1-adrenergic antagonist, [3HI-WB-4101. In renal olasma membranes obtained from the outer cortex of neonates,-the binding of the ligand was rapid, reversible, of high affinitv. saturable. and stereoselective. The com~etition studies " , with adrenergic agonists and antagonists were indicative of alphareceptors. In puppies less than 1-w-old, the binding affinity of 13H] -WB-4101 (Ka = 0.638 f 0.17 nM) was greater than 3-5 week-old puppies (Kd 1.573 + 0.315 nm); (P < 0.05), but receptor number was similar (63.75 + 19.1 versus 79.10 + 5.99 fmole/mg protein).N o consistent specific binding could be demonstrated in plasma membranes obtained from inner cortex or medulla. In the adult dog, no consistent specific binding could be demonstrated for plasma membranes obtained from any region of the kidney. These studies indicate that during maturation there is a decrease in alpha-adrenoceptor density and affinity in membranes from the outer cortex of the kidney.Recent studies have suggested that renal tubular sodium reabsorption may be modulated by renal nerve activity (4,5,7,9,27). The kidney is richly innervated by adrenergic nerves and the presence of dopamine-and norepinephrine-containing nerves have been demonstrated (1, 2, 10). The adrenergic nerves have been shown to be in direct contact with basement membrane of the proximal and distal tubules (1). Renal denervation decreases (4) and renal nerve stimulation increases (3) tubular sodium reabsorption. Several pathophysiologic conditions (denervation, salt loading) have been shown to alter norepinephrine and epinephrine levels in the kidney (22). In the rat (24) and dog (33) changes in sodium reabsorption have been related to alterations in alpha-adrenergic activity. In the isolated tubules of rabbits (5, 16) and mouse (26) however, increased sodium and chloride reabsorption (5, 16) in the proximal convoluted tubule, the thick ascending limb of Henle and the collecting duct followed administration of isoproterenol, a beta-adrenergic agonist. In addition, Bello-Reuss (5) showed that the increase in fluid (and presumably sodium) reabsorption in the proximal convoluted tubule induced by norepinephrine can be blocked by propranolol, a beta-adrenergic antagonist, but not by phenoxybenzamine, an alpha-adrenergic antagonist; thus, at least in the rabbit and mouse, betaadrenergic stimulation increases fluid transport. Dopamine, on the other hand, has been shown to decrease sodium reabsorption beyond the superficial distal tubule (25).Recently, specific adrenergic and dopaminergic receptors have been described in the kidney in several animal species (1 1, 12, 17, 18, 20, 21, 31). But no studies have characterized renal tubular alpha-adrenergic receptors in the dog, the species in which much of the physiologic data has been acquired. In order to understand further the role of alpha-adrenergic receptors...

Effects of Low-Dose Dopamine Infusion on Cardiovascular and Renal Functions, Cerebral Blood Flow, and Plasma Catecholamine Levels in Sick Preterm Neonates

“…clinical signs of stimulation of the a-adrenoreceptors and dopamine receptors occur before those of the 8-adrenoreceptors. Thus, the enhanced responsiveness of the preterm infant to the pressor effects of dopamine during the early postnatal period is mainly due to the increased a-adrenergic sensitivity of the immature cardiovascular system (22). However, the recently documented existence of a positive inotropic response (34) may also play a role in this phenomenon.…”

“…These mechanisms include this segment of the study reflecting an unpaired study design. maturation-dependent differences in the order of adrenergic Infants in the control group manifested clinical signs of poor receptor sensitivity (22), the unique hormonal milieu of preterm peripheral perfusion but had no systemic hypotension or signifinfants (I, 9,23), and immature metabolic function. We therefore icant oliguria (UV = 0.033 f 0.0 12 mL/min/kg).…”

Neonatal rabbit juxtamedullary proximal convoluted tubule acidification.

“…Furthermore, a change in transport during development may be due to tubular maturation or to developmental changes in the peritubular environment. Both peritubular physical forces and the hormonal milieu which may affect transport change during the first weeks of life (9)(10)(11)(12)(13)(14). The problems encountered in studying developmental changes in transport are averted by using in vitro microperfusion where a specific nephron segment can be studied under controlled conditions.…”

Effects of Epinephrine on the Renal Vascular Bed of Fetal, Newborn, and Adult Sheep

“…However, Jose et al (4) have shown that anesthetized puppies were more sensitive to intrarenal epinephrine than adults and had increased renal aadrenoceptor affinity and density compared to adult dogs (5).…”