Adenosine response of the rat kidney after saline loading, sodium restriction and hemorrhagia

Abstract

Experiments were performed on three groups of rats. The first group consisted of sodium loaded (SL) rats (high sodium diet, 10 meq Na/day, the second group consisted of sodium restricted (SR) rats (low sodium diet, 0.7 meq Na/day) and the third group consisted of hemorrhagic rats (HR), which were bled with 1-1,5% of the body weight. Blood pressure, glomerular filtration rate (GFR) and sodium excretion were measured. In some animals renal blood flow (RBF) was recorded with an electromagnetic flow meter. Adenosine was injected or infused into the thoracic aorta. Bolus injection of 10 nmoles adenosine resulted in a rapid and marked decrease of RBF (40%) in SR rats whereas in SL rats only a very small decrease of RBF (2%) was observed. Continuous infusion of adenosine (10(-7) moles/min) decreased GFR by 54% in SR rats and by 33% in HR rats, whereas GFR in SL rats did not change significantly. 5'-AMP decreased GFR in SR rats by 18% and in HR rats by 32%. Adenosine and 5'-AMP caused a slight fall in the systemic blood pressure, but this decrease could not account for the decrease of GFR. The sensitivity of kidney vasculature to adenosine parallelled high plasma renin activity (162 ng ang/ml-h in SR and 76 ng ang/ml-h in HR), elevated renal vascular resistance and low GFR. Simultaneous infusion of angiotensin (Hypertensin), 250 ng/min, in SL rats resulted in an increase of sensivity to adenosine infusion: GFR decreased by 21%. Our experiments demonstrated that a marked renal vasoconstriction caused by adenosine only occurs in rats in which renin-angiotensin system was stimulated.

Macula Densa Control of Renin Release and Glomerular Hemodynamics.

“…Under such circumstances, a further increase in adenosine levels by exogenous administration would not have any additional effect on afferent arterioles with macula densa attached. These observations are compatible with previous reports that adenosine decreases renin release in sodium-depleted animals (Tagawa and Vander 1970;Osswald et al 1975Osswald et al , 1978 but not in sodium-loaded animals (Osswald et al 1975(Osswald et al , 1978. Since endogenous adenosine levels are high in sodium-loaded animals, exogenous adenosine does not inhibit renin release further.…”

“…Osswald et al (1980) have shown that infusion of hypertonic saline into the thoracic aorta elevates renal tissue adenosine and decreases ATP, whereas increasing the sodium load to the kidney decreases renin release through a tubular mechanism involving the macula densa. In addition, intrarenal infusion of adenosine has been shown to decrease renin release in sodium-depleted animals (Tagawa and Vander 1970;Osswald et al 1975Osswald et al , 1978. Thus intrarenal formation of adenosine may play an important role in the control of renin release …”

RELEASE OF 3H‐PURINES FROM [3H]‐ADENINE LABELLED RABBIT KIDNEY FOLLOWING SYMPATHETIC NERVE STIMULATION, AND ITS INHIBITION BY α‐ADRENOCEPTOR BLOCKADE

“…From the results of experiments in the dog and rat it has been concluded that adenosine might play a role in the regulation of renal blood flow and glomerular filtration rate (Ono, Inagaki & Hashimoto, 1966;Tagawa & Vander, 1970;Haddy & Scott, 1971;Ueda, 1972;Osswald, Schmitz & Heidenreich, 1975). In addition to its direct vascular effects, adenosine potentiates the vasoconstrictor effect of noradrenaline (NA) (Hashimoto, 1971; and sympathetic nerve stimulation .…”

Role of Adenosine A1Receptor in Angiotensin II- and Norepinephrine-Induced Renal Vasoconstriction

“…Substantial experimental evidence supports the existence of a synergistic interaction between adenosine and the renin-angiotensin system in regulating renal hemodynamics (Hall et al, 1985;Hall and Granger, 1986;Wang et al, 1992;Munger and Jackson, 1994;Navar et al, 1996;Traynor et al, 1998). Early studies showed that suppression of the renin-angiotensin system by feeding a high-sodium diet (Osswald et al, 1975) or administration of an angiotensin-converting enzyme inhibitor (Hall et al, 1985) blunts the renal vasoconstrictor action of adenosine. Micropuncture studies (Munger and Jackson, 1994) have shown that angiotensin II type 1 receptor blockade with losartan markedly attenuates afferent arteriolar vasodilation induced by a selective adenosine A 1 receptor antagonist, 1,3-dipropyl-8-cyclopentylxanthine.…”