title: Interaction between AT1 and alpha1-adrenergic receptors in cardiomyopathic hamsters.
abstract: BACKGROUND
  Cross talk between angiotensin AT1 and alpha1-adrenergic receptors has been reported previously and points to the existence of physiologic regulation between the renin-angiotensin system and the sympathetic nervous system at the receptor level. This regulation may play an important role in the control of blood pressure and may be modified in different cardiovascular pathologies. Nevertheless, neither the physiologic actions nor the clinical relevance of the interaction between these 2 receptors has yet been established. To reveal these aspects in relation to heart failure, the interaction between vascular AT1 and alpha1-adrenergic receptors was evaluated in the Syrian cardiomyopathic hamster model.
  
  
  RESULTS
  The vascular response of each individual receptor to vasoactive agonist was assessed in the presence and absence of antagonists of the other receptor using aortic rings from 11-month-old Syrian cardiomyopathic hamsters. Age-matched golden hamsters were used as controls. In control hamsters, concentration-response curves for the norepinephrine (NE)-induced contraction were significantly displaced to the left after 100 mmol/L losartan incubation. The maximal tension achieved (Emax) values increased by 26+/-4.3% after incubation (P < .05). Similar results were obtained when 20 micromol/L enalapril was used to block angiotensin II (Ang II) synthesis. NE concentration-response curves were also displaced to the left and Emax increased by 27%+/-8.0% (P < .05). The concentrations that induce 50% of the maximal contraction (EC50) were 22.2+/-0.2 nmol/L for untreated and 27.1+/-2.0 nmol/L for losartan-treated aortic rings (n = 8, P > .05). However, EC50 values were significantly reduced in aortic rings treated with enalapril (7.51+/-0.16 nmol/L, n = 8, P < .05). Blockade of alpha1 receptor with 10 micromol/L prazosin increased the response to Ang II by 32% (n = 6, P < .05). In contrast, when these experiments were repeated in aortic rings from cardiomyopathic animals, no interaction between the 2 receptors was observed. NE concentration-response curves, Emax (9.6%+/-2.8% increase after enalapril. and 5.8%+/-6.5% increase after losartan, P > .05) and EC50 values (14.7+/-0.7 nmol/L without treatment, 17.5+/-1.5 nmol/L with enalapril and 11.1+/-0.8 with losartan, n = 8, P > .05) were similar. Furthermore, in cardiomyopathic animals, prazosin did not modify the vascular response to Ang II.
  
  
  CONCLUSIONS
  An interaction exists between vascular AT1 and alpha1-adrenergic receptors in control hamsters but not in cardiomyopathic animals. This interaction seems to be bidirectional and counterregulatory. The lack of this regulation may promote a state of enhanced vascular wall activity, which could contribute to the increased vasoconstriction and total peripheral resistance characteristic of heart failure.
authors.affiliation: Department of Pharmacology, University of Puerto Rico-School of Medicine, San Juan 00936-5067, USA.
authors.forename: M J
authors.initials: MJ
authors.lastname: Crespo
mesh_terms: D000803:Angiotensin I / Q000378:metabolism*; D000818:Animals; D000959:Antihypertensive Agents / Q000494:pharmacology*; D001011:Aorta / Q000187:drug effects; D009202:Cardiomyopathies / Q000378:metabolism* / Q000503:physiopathology; D006224:Cricetinae; D004195:Disease Models, Animal; D004656:Enalapril / Q000494:pharmacology; D006801:Humans; D019808:Losartan / Q000494:pharmacology; D008297:Male; D008647:Mesocricetus; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects* / Q000378:metabolism; D011224:Prazosin / Q000494:pharmacology; D020239:Receptor Cross-Talk; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects*; D011945:Receptors, Angiotensin / Q000187:drug effects*; D014655:Vascular Resistance
chemical_list: D000959:Antihypertensive Agents; D018340:Receptors, Adrenergic, alpha-1; D011945:Receptors, Angiotensin; D004656:Enalapril; D000803:Angiotensin I; D019808:Losartan; D011224:Prazosin