Neural effects on renal blood flow during acute hypotension vary with antihypertensive drugs.
To examine the neural effects of antihypertensive drugs on renal blood flow, we measured blood flow and renal sympathetic nerve activity simultaneously in conscious spontaneously hypertensive rats aged 13 to 15 weeks. One to two days after surgery, intravenous administration of manidipine (calcium antagonist, n = 10), doxazosin (alpha 1-adrenergic receptor antagonist, n = 9), and clonidine (n = 7) lowered mean arterial pressure by at least 20% from baseline levels. Manidipine initiated a reduction of renal blood flow when mean pressure decreased by 20 +/- 2 mm Hg. At the maximal decrease in renal blood flow (mean pressure, -33 +/- 2 mm Hg), percent decrease in flow (-27 +/- 2%) significantly correlated with percent increase in renal nerve activity (+205 +/- 40%, r = -.878). Doxazosin began to decrease renal blood flow at a level of arterial pressure similar to that in manidipine treatment, whereas the maximal decrease in flow (-19 +/- 2%; mean pressure, -33 +/- 2 mm Hg; nerve activity, +225 +/- 44%) was significantly less than that in manidipine treatment. Although clonidine decreased arterial pressure and renal nerve activity, renal blood flow did not decrease even at the maximal decrease in mean pressure of 29 +/- 1 mm Hg. The addition of clonidine to manidipine treatment suppressed reflexly enhanced renal nerve activity and restored blood flow to the pretreatment level despite pronounced hypotension. These results clearly demonstrate that antihypertensive drugs with blocking action on renal nerve activity are capable of maintaining renal blood flow and that those associated with reflex-induced enhancement of nerve activity exert deteriorating effects on renal blood flow. Furthermore, a decrease in renal blood flow induced by calcium antagonists is mainly attributed to reflexly enhanced renal nerve activity.
Takishita
S
S
Third Department of Internal Medicine, University of the Ryukyus School of Medicine, Okinawa, Japan.
Muratani
H
H
Kawazoe
N
N
Kimura
Y
Y
Tozawa
M
M
Fukiyama
K
K
D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D003000:Clonidine / Q000494:pharmacology*; D004095:Dihydropyridines / Q000494:pharmacology*; D017292:Doxazosin / Q000494:pharmacology*; D007022:Hypotension / Q000139:chemically induced / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000294:innervation; D008297:Male; D009578:Nitrobenzenes; D010879:Piperazines; D051381:Rats; D011918:Rats, Inbred SHR; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012044:Regression Analysis; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000502:physiology*; D013997:Time Factors
D000959:Antihypertensive Agents; D004095:Dihydropyridines; D009578:Nitrobenzenes; D010879:Piperazines; C054218:manidipine; D003000:Clonidine; D017292:Doxazosin