Central endogenous histamine modulates sympathetic outflow through H3 receptors in the conscious rabbit.
1. This study examined the role of histamine H(3) receptors in vagal and sympathetic autonomic reflexes in the conscious rabbit, and in rabbit and guinea-pig isolated right atria. 2. The baroreceptor-heart rate reflex (baroreflex), Bezold-Jarisch-like and nasopharyngeal reflexes were assessed after these treatments (i.v.; with H(1) and H(2) receptor block): (i) vehicle (saline; n=11); (ii) H(3) receptor agonist, (R)-alpha-methylhistamine (R-alpha-MH) 100 micro g kg(-1)+100 micro g kg(-1) h(-1) (n=9); (iii) H(3) receptor antagonist, thioperamide 1 mg kg(-1)+1 mg kg(-1) h(-1) (n=11); (iv) R-alpha-MH and thioperamide (n=6); and (v) H(2) and H(3) antagonist, burimamide 6.3 mg kg(-1)+6.3 mg kg(-1) h(-1) (n=4). 3. R-alpha-MH caused a thioperamide-sensitive fall in mean arterial pressure (MAP) of 8+/-1 mmHg and tachycardia of 18+/-2 bpm (P<0.0005). Burimamide was without effect, however thioperamide elicited an increase in MAP of 4+/-1 mmHg (P<0.01), but no change in heart rate (HR). 4. R-alpha-MH caused a 44% decrease in the average gain of the baroreflex (P=0.0001); this effect was antagonised by thioperamide. Thioperamide caused a parallel rightward shift in the barocurve with an increase in MAP of 5 mmHg (P<0.05). Burimamide had no effect on the baroreflex. The vagally mediated bradycardia elicited by the Bezold-Jarisch and nasopharyngeal reflexes was unaffected by H(3) receptor ligand administration. 5. R-alpha-MH (<or=10 micro M) caused a thioperamide-sensitive depression of both sympathetic and vagal responses in guinea-pig atria, but had no effect in rabbit atria. 6. As H(3) receptor activation caused a significant decrease in baroreflex gain without affecting HR range, the former is unlikely to be simply due to peripheral sympatholysis (supported by the lack of effect in isolated atria). Central H(3) receptors may have a tonic role in the baroreflex as thioperamide caused a rightward resetting of the barocurve. In contrast, the peripherally acting H(3) antagonist burimamide was without effect. These findings suggest a role for central histamine H(3) receptors in cardiovascular homeostasis in the rabbit.
Charles
Julian
J
Department of Pharmacology, The University of Melbourne, Victoria 3010, Australia.
Angus
James A
JA
Wright
Christine E
CE
D000320:Adrenergic Fibers / Q000187:drug effects / Q000378:metabolism*; D000818:Animals; D017704:Baroreflex / Q000187:drug effects / Q000502:physiology; D003243:Consciousness / Q000187:drug effects / Q000502:physiology*; D004305:Dose-Response Relationship, Drug; D005260:Female; D006168:Guinea Pigs; D006325:Heart Atria / Q000187:drug effects / Q000378:metabolism; D006632:Histamine / Q000378:metabolism* / Q000494:pharmacology; D006633:Histamine Antagonists / Q000494:pharmacology; D066298:In Vitro Techniques; D008297:Male; D011817:Rabbits; D018100:Receptors, Histamine H3 / Q000378:metabolism*
D006633:Histamine Antagonists; D018100:Receptors, Histamine H3; D006632:Histamine