title: Structural factors increase blood pressure through the interaction of resistance vessel geometry with neurohumoral and local factors: estimates in rabbits with renal cellophane-wrap hypertension with intact effectors and during neurohumoral blockade.
abstract: BACKGROUND
  The structural changes in hypertension include narrowing of the lumen of the large resistance vessels and an increase in their wall thickness : lumen ratio. Their haemodynamic role has been controversial.
  
  
  OBJECTIVE
  To examine resting haemodynamics and the responses to graded drug-induced changes in tone in renal cellophane-wrap (wrap) and sham-operated (sham) rabbits, when their neurohumoral effectors were intact and during high-level blockade.
  
  
  METHODS
  Each rabbit was implanted with a flow probe for measuring cardiac output, had catheters inserted for drug infusions, and underwent mean arterial pressure (MAP) measurements. Resting values were determined and we infused graded doses of dilator and constrictor drugs: acetylcholine or adenosine; angiotensin II or methoxamine. The dilator and constrictor dose-response curves were combined into a single relationship for MAP, cardiac output, total peripheral conductance (TPC) and heart rate; total peripheral resistance (TPR) was estimated as 1/TPC.
  
  
  RESULTS
  Throughout the range of vascular tone and with intact effector function, MAP was greater and TPC lower in wrap than in sham rabbits, and cardiac output was the same in both groups. The ratios of wrap : sham slopes of the log dose-response regression lines were 0.47 for TPC, 2.04 for TPR and 1.89 for MAP. Thus MAP and TPR responses were enhanced to the same degree in wrap rabbits. During neurohumoral block, baroreflex-mediated heart rate responses were abolished. In addition, resting vascular tone was lower than with intact effectors in both wrap and sham rabbits; however, the ratios of wrap : sham slopes for TPC and TPR were similar to those with intact effectors, whereas the ratio for the slope for MAP was slightly smaller, although still enhanced.
  
  
  CONCLUSIONS
  In wrap hypertension, the enhanced MAP and TPR responses are in accord with an interaction between vascular geometry and the sum of altered neurohumoral + local activity, plus a rarefaction component.
authors.affiliation: Department of Pharmacology, University of Melbourne, Australia. cewright@unimelb.edu.au
authors.forename: Christine E
authors.initials: CE
authors.lastname: Wright
authors.forename: James A
authors.initials: JA
authors.lastname: Angus
authors.forename: Paul I
authors.initials: PI
authors.lastname: Korner
mesh_terms: D000241:Adenosine / Q000008:administration & dosage / Q000494:pharmacology; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002476:Cellophane; D004305:Dose-Response Relationship, Drug; D005260:Female; D006339:Heart Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006973:Hypertension / Q000209:etiology* / Q000503:physiopathology*; D007668:Kidney; D008297:Male; D008729:Methoxamine / Q000008:administration & dosage / Q000494:pharmacology; D018377:Neurotransmitter Agents / Q000037:antagonists & inhibitors / Q000502:physiology*; D011817:Rabbits; D012018:Reflex / Q000502:physiology; D014655:Vascular Resistance / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000008:administration & dosage / Q000494:pharmacology; D014665:Vasodilator Agents / Q000008:administration & dosage / Q000494:pharmacology
chemical_list: D018377:Neurotransmitter Agents; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D002476:Cellophane; D008729:Methoxamine; D000241:Adenosine