Differing effects of enalapril and losartan on renal medullary blood flow and renal interstitial hydrostatic pressure in spontaneously hypertensive rats.
OBJECTIVE
To determine the effect of short-term angiotensin converting enzyme inhibition (enalapril) or angiotensin II AT1 receptor blockade (losartan) on medullary hemodynamics in the spontaneously hypertensive rat (SHR).


METHODS
Laser-Doppler flowmetry allowed for the characterization of medullary blood flow (MBF) over a wide range of renal arterial pressure (RAP), and was used for comparison among treatment groups. Renal interstitial hydrostatic pressure (RIHP) was also determined over a wide range of RAP.


METHODS
Enalapril or losartan was given to male 12-13-week-old SHR for 3 days (25 mg/kg per day in drinking water). Rats were anesthetized with Inactin, renal function was measured at resting levels of RAP and then RAP was varied over a range of 50-150 mmHg in 25 mmHg steps. MBF and RIHP were determined at each pressure.


RESULTS
Resting mean arterial pressure (MAP) (mmHg +/- SE) for enalapril- and for losartan-treated SHR [114 +/- 3 (n = 18) and 124 +/- 3 (n = 20), respectively] were both significantly lower than for untreated SHR [159 +/- 5 (n = 20)]. Renal function at resting levels of MAP was not significantly different among groups. Enalapril and losartan both increased MBF by 30% at levels of RAP of 125 mmHg and over. Enalapril did not alter the relation between RAP and RIHP, but losartan shifted the RAP versus RIHP curve by approximately 40 mmHg to lower levels of RAP. Acute administration of the B2 kinin receptor antagonist HOE 140 [20 microg/kg intravenous (i.v.) bolus, then 10 microg/kg per h i.v.] did not significantly alter MAP in any group. HOE 140 did not significantly alter MBF or RIHP in the untreated or losartan-treated SHR. MBF in enalapril-treated rats receiving HOE 140 was not significantly different from that of the enalapril-only group; however, the relation between RAP and RIHP was shifted to lower levels of RAP by approximately 45 mmHg.


CONCLUSIONS
Both enalapril and losartan increase MBF in SHR, suggesting that the medullary circulation of SHR is influenced by endogenous levels of angiotensin II. The failure of enalapril to increase RIHP in parallel with MBF appears to be due to an enhanced effect of kinins.
Dukacz
S A
SA
Department of Physiology, The University of Western Ontario, London, Canada.
Kline
R L
RL
D000319:Adrenergic beta-Antagonists / Q000494:pharmacology; D000803:Angiotensin I / Q000494:pharmacology; D000804:Angiotensin II / Q000494:pharmacology; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D001920:Bradykinin / Q000031:analogs & derivatives / Q000494:pharmacology; D004656:Enalapril / Q000494:pharmacology*; D006874:Hydrostatic Pressure; D007679:Kidney Medulla / Q000098:blood supply / Q000187:drug effects*; D017078:Laser-Doppler Flowmetry; D019808:Losartan / Q000494:pharmacology*; D008297:Male; D051381:Rats; D011918:Rats, Inbred SHR; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D012079:Renal Circulation / Q000187:drug effects*
D000319:Adrenergic beta-Antagonists; D057911:Angiotensin Receptor Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D044140:Receptor, Angiotensin, Type 1; D044139:Receptor, Angiotensin, Type 2; D000804:Angiotensin II; D004656:Enalapril; C065679:icatibant; D000803:Angiotensin I; D019808:Losartan; D001920:Bradykinin