Short-term effects of angiotensin II blockade on renal blood flow and sympathetic activity in awake rats.
To investigate the effects of an angiotensin II type 1 receptor antagonist (CV-11974) on renal blood flow and renal sympathetic nerve activity compared with a calcium antagonist (nicardipine), we measured both parameters in conscious spontaneously hypertensive rats aged 13 to 15 weeks. One to 2 days after surgery, CV-11974 (n = 9) and nicardipine (n = 8) were intravenously administered to decrease arterial pressure in a similar time course and degree of hypotension. CV-11974 increased renal blood flow by 23 +/- 4% at the maximal fall in mean arterial pressure (-32 +/- 1 mm Hg), and renal nerve activity increased by 70 +/- 7%. The maximal increase in renal blood flow (+27 +/- 4%) was observed when mean pressure was reduced by approximately 20 mm Hg. The maximal reduction of renal vascular resistance (-33 +/- 3%) correlated significantly with pretreatment levels of plasma renin concentration (r = -.792). In contrast, nicardipine produced a progressive reduction of renal blood flow and marked increases in heart rate and renal nerve activity. Increases in heart rate and nerve activity were greater than those with CV-11974 treatment (P < .001). At the maximal fall in mean pressure (-32 +/- 1 mm Hg), renal blood flow decreased by 23 +/- 4%, which was significantly correlated with percent changes in renal nerve activity (+150 +/- 11%, r = -.744). Renal denervation in another set of rats (n = 6) improved renal blood flow and renal vascular resistance responses to nicardipine.(ABSTRACT TRUNCATED AT 250 WORDS)
Takishita
S
S
Third Department of Internal Medicine, University of The Ryukyus School of Medicine, Okinawa, Japan.
Muratani
H
H
Sesoko
S
S
Teruya
H
H
Tozawa
M
M
Fukiyama
K
K
Inada
Y
Y
D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001562:Benzimidazoles / Q000494:pharmacology*; D001713:Biphenyl Compounds; D001794:Blood Pressure / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006973:Hypertension / Q000503:physiopathology; D007668:Kidney / Q000187:drug effects / Q000294:innervation; D008297:Male; D009529:Nicardipine / Q000494:pharmacology*; D051381:Rats; D011918:Rats, Inbred SHR; D012079:Renal Circulation / Q000187:drug effects*; D013562:Sympathectomy; D013564:Sympathetic Nervous System / Q000187:drug effects*; D013777:Tetrazoles / Q000494:pharmacology*
D057911:Angiotensin Receptor Antagonists; D001562:Benzimidazoles; D001713:Biphenyl Compounds; D013777:Tetrazoles; D009529:Nicardipine; C081643:candesartan