Peripheral presynaptic facilitatory effect of angiotensin II on noradrenaline release in anesthetized rabbits.
The function of presynaptic angiotensin II receptors at postganglionic sympathetic terminal axons under conditions of uninterrupted sympathetic impulse traffic was studied in anesthetized rabbits (alfadolone + alfaxalone). Mean arterial pressure, postganglionic renal sympathetic firing rate, the arterial plasma noradrenaline concentration, and heart rate were measured before (basal values) and at the end of 4-min infusions of sodium nitroprusside. Angiotensin II (20 or 100 ng kg-1 min-1) caused dose-dependent increases of basal mean arterial pressure and decreases of basal sympathetic nerve activity and heart rate, but did not change the basal plasma noradrenaline concentration. Moreover, it shifted the sympathetic nerve activity-plasma noradrenaline relationship in a manner indicating an increase of the average release of noradrenaline per action potential. Angiotensin II at 100 ng kg-1 min-1 had an additional effect, at any given blood pressure, sympathetic nerve activity and heart rate were lower than in the controls. Captopril (1 mg kg-1 followed by 1 mg kg-1 h-1) caused no change in any parameter. The results demonstrate that exogenous angiotensin II activates release-facilitating receptors at postganglionic sympathetic neurons in rabbits with ongoing sympathetic nerve activity. Endogenous angiotensin II, however, played no role in cardiovascular regulation under the present, acute experimental conditions. Vasopressin, which was studied for comparison, lacked a presynaptic effect on the release of noradrenaline but caused sympathoinhibition by an action on a central component of the baroreflex.
Pharmakologisches Institut der Universität, Freiburg, Federal Republic of Germany.
B
B
Szabo
L
L
Hedler
C
C
Schurr
K
K
Starke
D000758:Anesthesia; D000804:Angiotensin II / Q000378:metabolism / Q000494:pharmacology*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002216:Captopril / Q000494:pharmacology; D006339:Heart Rate / Q000187:drug effects; D066298:In Vitro Techniques; D007668:Kidney / Q000294:innervation / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D009638:Norepinephrine / Q000097:blood / Q000378:metabolism*; D011817:Rabbits; D011945:Receptors, Angiotensin / Q000378:metabolism; D013564:Sympathetic Nervous System / Q000187:drug effects; D013569:Synapses / Q000187:drug effects / Q000378:metabolism*; D014667:Vasopressins / Q000494:pharmacology
D011945:Receptors, Angiotensin; D014667:Vasopressins; D000804:Angiotensin II; D009599:Nitroprusside; D002216:Captopril; D009638:Norepinephrine