Sodium depletion in conscious cynomolgus monkeys attenuates baroreflex sensitivity independently of prostaglandins.
We tested the hypothesis that baroreflex attenuation during sodium depletion is due to increased prostaglandin (PG) levels. We studied baroreflex sensitivity before and after PG synthesis inhibition in conscious cynomolgus monkeys. Arterial pressure and pulse interval (PI) were measured during intravenous infusions of phenylephrine (1-20 micrograms.kg-1.min-1, n = 6) and nitroprusside (1-10 micrograms.kg-1.min-1, n = 7). Infusions were repeated 30 min after indomethacin (Indo, 6 mg/kg iv). The slope (in ms/mmHg) of the mean arterial blood pressure-PI plot was used as an index of baroreflex sensitivity. Plasma renin activity (PRA) was elevated (47.9 +/- 9.7 vs. 8.8 +/- 3.3 ng angiotensin I.ml-1.h-1) after sodium depletion (P < 0.05). Baroreflex sensitivity to hypotension and hypertension was significantly (P < 0.05) attenuated by sodium depletion (3.69 +/- 0.9 vs. 0.9 +/- 0.1 ms/mmHg and 7.38 +/- 0.6 vs. 5.04 +/- 0.9 ms/mmHg, respectively). Indo decreased PRA to 28.6 +/- 5.7 ng angiotensin I.ml-1.h-1 (P < 0.05) in sodium-depleted monkeys and decreased heart rate -21 +/- 3.7 from a baseline of 166 +/- 9.40 beats/min in normal monkeys and -22 +/- 2.9 from a baseline of 191 +/- 7.9 beats/min in low-sodium monkeys (P < 0.05). Indo did not significantly change baroreflex sensitivity in either group. Thus the baroreflex was attenuated in conscious nonhuman primates during sodium depletion; acute PG synthesis blockade did not improve baroreflex sensitivity. Indo decreased heart rate without changing arterial pressure; suggesting that PGs caused a downward resetting of the pressure-heart rate relationship.
Pharmacology Department, Boehringer Ingelheim Pharmaceuticals, Ridgefield, Connecticut 06877-0368.
M J
MJ
Panzenbeck
P C
PC
Harrison
J B
JB
Madwed
M L
ML
McFarland
R J
RJ
Winquist
P
P
Frei
S
S
Weldon
S N
SN
Desai
D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology*; D001794:Blood Pressure / Q000187:drug effects; D004039:Diet, Sodium-Restricted; D007213:Indomethacin / Q000494:pharmacology; D008252:Macaca fascicularis; D008297:Male; D009599:Nitroprusside / Q000494:pharmacology; D010656:Phenylephrine / Q000494:pharmacology; D011453:Prostaglandins / Q000097:blood*; D011674:Pulse / Q000187:drug effects; D012083:Renin / Q000097:blood; D012964:Sodium / Q000172:deficiency*; D000092502:Renin Inhibitors
D007213:Indomethacin; D009599:Nitroprusside; D010656:Phenylephrine; D011453:Prostaglandins; D012083:Renin; D012964:Sodium; D000092502:Renin Inhibitors