Effects of erythropoietin administration on blood pressure and urinary albumin excretion in rats.

The effects of recombinant human erythropoietin (rHuEPO) administration on blood pressure and urinary albumin excretion were studied in normotensive Wistar-Kyoto rats (WKY), in spontaneously hypertensive rats (SHR), and in SHR rats treated with an angiotensin converting enzyme inhibitor (SHR-ACEi). Rats were housed in metabolic cages and treated with rHuEPO (150 U/kg body weight [bw] three times a week) for 6 weeks. Control animals received the vehicle only (0.25 mL of physiological saline). An angiotensin converting enzyme inhibitor was administered in the drinking water for 6 weeks (spirapril 5 mg/kg bw). Systolic blood pressure (SBP), and 24 h urinary albumin excretion (UAE) were measured once a week. No significant differences in SBP were observed between rHuEPO and vehicle-treated normotensive animals at the end of the treatment (171.9 +/- 4.9 v 172.1 +/- 5.6 mm Hg, respectively). After 6 weeks, SBP was significantly higher in SHR and SHR-ACEi groups treated with rHuEPO than in control groups (239.8 +/- 7.3 and 243.0 +/- 7.3 mm Hg v 218.1 +/- 6.0 and 187.9 +/- 4.6 mm Hg, respectively); UAE was significantly higher in groups treated with rHuEPO than in control groups (WKY: 265.9 +/- 19.5 v 127.0 +/- 12.3 microg/100 g bw, SHR: 1668.4 +/- 564.6 v 234.8 +/- 22.9 microg/100 g bw, and SHR-ACEi: 1522.7 +/- 448.3 v 143.0 +/- 18.9 microg/100 g bw, respectively). We concluded that erythropoietin treatment causes an increase in arterial pressure in SHR only, and an increase in UAE in both normotensive and hypertensive rats. The albuminuric effect was not entirely dependent on increased blood pressure. The treatment with an angiotensin converting enzyme inhibitor did not modify either the proteinuric or the pressor effects.

Effects of adenosine receptor agonists on renal function in anaesthetized rats.

OBJECTIVES: To investigate the effects of the interaction between adenosine receptors and renal nerves on urinary sodium excretion and glomerular filtration rate. METHODS AND DESIGN: The effects on water and sodium excretion and glomerular filtration rate of A1 [2-chloro-N6-cyclopentyl-adenosine (CCPA)] and A2 [2-hesinyl-5'-N-ethyl-carboxamido-adenosine (2HE-NECA)] adenosine agonists were studied in anaesthetized rats with one kidney surgically denervated. Arterial blood pressure, heart rate and rate of urine flow from each kidney were continuously recorded; inulin clearance was used as an index of glomerular filtration rate. The experiments were performed with three groups of rats, into which, after a control period of 20 min, CCPA, 2HE-NECA or vehicle was infused for two subsequent 20 min periods. RESULT: During infusion of CCPA, the slight decrease in arterial pressure was associated with a transient decrease in glomerular filtration rate and marked long-lasting decreases in heart rate, water and sodium excretion and fractional sodium excretion. The response of the innervated kidney was similar to the response of the denervated kidney. Infusion of 2HE-NECA caused decreases in arterial pressure, glomerular filtration rate and excretion of water and sodium associated with an increase in heart rate. The reduction of water and sodium excretion from the innervated kidney was larger than that from the denervated kidney. CONCLUSIONS: Activation both of A1 and of A2 receptor causes a reduction in urinary water and sodium excretion. The renal response to activation of A2 receptors is enhanced by the presence of renal nerves, whereas the response to activation of A1 receptors is not influenced by renal nerves.

Effects of adenosine-receptor agonists on renin release in anaesthetized rats.

OBJECTIVE: To investigate the effects of the interaction between adenosine receptors and renal nerves on renin release. MATERIALS AND METHODS: The effects on renin secretion of A1 (2-chloro-N6-cyclopentiladenosine) and A2 (2-hexynil-5'-N-ethyl-carboxamido-adenosine) adenosine-receptor agonists were studied in two groups of anaesthetized rats, each with one kidney surgically denervated. Arterial blood pressure and the renal blood flow of innervated and denervated kidneys were continuously recorded. Cannulae were inserted into both renal veins through femoral veins. After 1h of rest, A1 and A2 agonists were intravenously infused for 30 min in the two groups of rats. Plasma renin activity was measured by radioimmunoassay in blood samples drawn simultaneously from both renal veins and the femoral artery before and after the drug infusion. RESULTS: Infusions of A1 and A2 agonists produced comparable hypotensive effects. During A1 agonist administration, the heart rate decreased significantly, but it did not change after A2 agonist treatment. Renal blood flow was reduced by administration of the A1 agonist in both kidneys, while A2 agonist administration significantly reduced the renal blood flow of the innervated kidney only. The veno-arterial difference in plasma renin activity decreased after the A1 agonist infusion in both kidneys, but after the A2 agonist infusion it increased significantly in the innervated kidney only. CONCLUSIONS: Renal nerves do not influence the inhibition of renin release mediated by A1 adenosine receptors. In vivo, A2-receptor agonist administration can stimulate renin release only in the presence of intact renal nerves.