Sympathetic responses to stress and rilmenidine in 2K1C rabbits: evidence of enhanced nonvascular effector mechanism.
We determined whether the sympathetic excitatory responses to environmental stressors and the sympathoinhibitory responses to rilmenidine are altered by renovascular hypertension. Rabbits were made hypertensive with a clip on the right renal artery, and a left renal nerve recording electrode was implanted. After 3 or 6 weeks, the animals were given air-jet stress and loud noise stress before and after intravenous rilmenidine. Three and 6 weeks after renal clipping, mean arterial pressure was 28% and 36% greater than preclip values. Air-jet stress elicited a marked increase in renal sympathetic nerve activity, mean arterial pressure, and heart rate. Renal sympathetic nerve activity responses were much greater in hypertensive rabbits, but the pressor responses were similar to those observed in normotensive animals. Acute administration of rilmenidine decreased blood pressure more in hypertensive animals but with a much lesser inhibition of sympathetic activity. Rilmenidine markedly reduced increased sympathetic activity during air-jet stress in 3-week clipped rabbits but to a lesser extent in the other groups. These studies show that while sympathetic responses to stress were markedly enhanced in renal clip hypertensive rabbits, they did not result in greater pressor responses, thus suggesting that vascular neuroeffector mechanisms were not altered. By contrast, the increased effects of rilmenidine suggest a much greater contribution to the hypertension by the sympathetic nervous system, but one that is caused by an enhanced "nonvascular" neuroeffector mechanism. As such, sympathoinhibitory agents such as rilmenidine are very suitable and very effective agents for the treatment of renovascular hypertension.
Head
Geoffrey A
GA
Baker Heart Research Institute, Commercial Road Prahran, St. Kilda Road Central, Melbourne, Victoria, 8008, Australia. geoff.head@baker.edu.au
Burke
Sandra L
SL
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006978:Hypertension, Renovascular / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D007668:Kidney / Q000294:innervation* / Q000473:pathology; D008297:Male; D009929:Organ Size; D010080:Oxazoles / Q000494:pharmacology*; D011817:Rabbits; D000077769:Rilmenidine; D013312:Stress, Physiological / Q000150:complications; D013564:Sympathetic Nervous System / Q000187:drug effects / Q000503:physiopathology*
D010080:Oxazoles; D000077769:Rilmenidine