A new approach to assessing the structural total peripheral resistance amplifier in renal (Page) hypertension in conscious rabbits.
OBJECTIVE
Structural changes in the large resistance vessels in hypertension amplify resistance responses in vitro, but their role in vivo has been controversial. To resolve this matter, we re-examined earlier data in Page hypertension.


METHODS
Total peripheral resistance (TPR) and total peripheral conductance (TPC) responsiveness were compared in hypertensive and normotensive rabbits, 5 weeks after bilateral renal cellophane wrapping or sham operation. The rabbits were studied with effectors intact; during ganglionic blockade; during neurohumoral blockade (NHB). For each condition extended scaled dose (ScD)-TPC and TPR curves were derived from individual dose-response curves to two constrictors and two dilators.


RESULTS
The ScD-response curves had two major nonlinearities: at high constrictor doses, due to functional (reversible) rarefaction (reduction in microcirculatory density); at high dilator doses, due to impaired autoregulation. The amplifier is best assessed during NHB over the intervening ScD range, by determining the TPR and TPC ratios from hypertensive and normotensive rabbits. Over this range the hypertensive: normotensive (H: N) ratio averaged 1.88 +/- 0.03 TPR units and was the same for constrictor and dilator responses, suggesting a structural basis; the resting H: N TPR ratio was also closely similar. At higher ScDs functional rarefaction developed initially at a greater rate in normotensive than in hypertensive rabbits. We conjecture that this was because some permanent rarefaction had already developed in hypertensive rabbits since the onset of hypertension.


CONCLUSIONS
The systemic structural TPR amplifier is haemodynamically important in vivo and contributes to hypertension.
Korner
Paul I
PI
Department of Pharmacology, University of Melbourne, Victoria 3010, Australia.
Wright
Christine E
CE
Angus
James A
JA
D000109:Acetylcholine / Q000008:administration & dosage; D000241:Adenosine / Q000008:administration & dosage; D000804:Angiotensin II / Q000008:administration & dosage; D000818:Animals; D001808:Blood Vessels / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D002476:Cellophane; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D005260:Female; D005730:Ganglionic Blockers / Q000008:administration & dosage; D006977:Hypertension, Renal / Q000209:etiology / Q000473:pathology / Q000503:physiopathology*; D008297:Male; D008729:Methoxamine / Q000008:administration & dosage; D011817:Rabbits; D014655:Vascular Resistance / Q000187:drug effects / Q000502:physiology*; D014662:Vasoconstrictor Agents / Q000008:administration & dosage; D014665:Vasodilator Agents / Q000008:administration & dosage
D005730:Ganglionic Blockers; D014662:Vasoconstrictor Agents; D014665:Vasodilator Agents; D000804:Angiotensin II; D002476:Cellophane; D008729:Methoxamine; D000241:Adenosine; D000109:Acetylcholine