Renal vascular effects of frusemide in the rat: influence of salt loading and the role of angiotensin II.
We showed recently that post-frusemide (furosemide) natriuresis was associated with a major depression of medullary circulation. In the present study, prior to administration of frusemide the tubular transport of NaCl was modified by loading the animals with 5% saline to elucidate a possible interrelation between the tubular and vascular effects of the drug. Moreover, a possible involvement of the renin-angiotensin system was examined by pharmacological blockade using captopril, an inhibitor of angiotensin converting enzyme (1 mg x kg(-1), I.V.), or losartan, a selective inhibitor of angiotensin AT1 receptor (10 mg x kg(-1), I.V.). The effects of frusemide (0.25 mg x kg(-1) I.V., then the same dose given over 1 h) on renal medullary and cortical circulation (using laser-Doppler flowmetry) and renal excretion of sodium (U(Na)V), water and total solutes were measured in anaesthetised rats. With no pre-treatment, frusemide decreased the medullary flow (36.6 +/- 6.0%) significantly more than the cortical flow (10.1 +/- 1.0%; P < 0.001). The difference between the medulla and cortex was not significant in rats which showed high U(Na)V after hypertonic saline loading (2.0 +/- 0.4 vs. 0.4 +/- 0.1 micromol x min(-1) in non-loaded rats): 21.1 +/- 3.9% and 15.8 +/- 1.5%, respectively. At very high U(Na)V (9.5 +/- 1.1 micromol x min(-1)) the post-frusemide decrease in blood flow tended to be smaller in the medulla (7.6 +/- 7.7%) than in the cortex (16.2 +/- 2.6%). The fall in medullary blood flow was attenuated by pre-treatment with captopril (22.0 +/- 3.3%) and abolished by pre-treatment with losartan (2.8 +/- 11.8%). The decrease in cortical blood flow was not changed by hypertonic saline or angiotensin II blockers. The abolition of the post-frusemide depression of medullary blood flow by previous salt loading confirms the proposed link between tubular transport status and vasoconstriction. A similar modification of the response by blockade of the renin-angiotensin system suggests that the system is involved in the mechanism of medullary vasoconstriction.
Dobrowolski
L
L
Laboratory of Renal and Body Fluid Physiology, Medical Research Centre of the Polish Academy of Sciences, Pawiñskiego 5, 02-106 Warsaw, Poland. renal@cmdik.pan.pl
Badzyńska
B
B
Grzelec-Mojzesowicz
M
M
Sadowski
J
J
D000704:Analysis of Variance; D000804:Angiotensin II / Q000378:metabolism*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology; D001692:Biological Transport / Q000502:physiology; D002216:Captopril / Q000494:pharmacology; D004232:Diuretics / Q000494:pharmacology; D005665:Furosemide / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply / Q000502:physiology*; D007684:Kidney Tubules / Q000187:drug effects* / Q000378:metabolism; D017078:Laser-Doppler Flowmetry; D019808:Losartan / Q000494:pharmacology; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D012079:Renal Circulation / Q000502:physiology*; D012964:Sodium / Q000652:urine; D012965:Sodium Chloride / Q000378:metabolism*; D013997:Time Factors; D014554:Urination; D014661:Vasoconstriction / Q000187:drug effects* / Q000502:physiology
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D004232:Diuretics; D000804:Angiotensin II; D012965:Sodium Chloride; D005665:Furosemide; D002216:Captopril; D012964:Sodium; D019808:Losartan