Long-term effects of brief antihypertensive treatment on systolic blood pressure and vascular reactivity in young genetically hypertensive rats.
Recent studies have shown that angiotensin converting enzyme (ACE) inhibitor treatment in young spontaneously hypertensive rats (SHR) reduces blood pressure into adulthood. This study explored changes in vascular reactivity in adult normotensive (WKY) rats and stroke-prone SHR (SHRSP) receiving the following treatments at 6-10 weeks of age: (a) ACE inhibitor (ramipril); (b) hydralazine/hydrochlorothiazide (hydral/HCTZ); or (c) no treatment. The hypothesis tested was that vascular changes and blood pressure would be reduced in adult SHRSP treated with ramipril during development. At 17 weeks of age, rats were anesthetized and vascular tissue was excised. Isolated experiments in the aorta included characterization of initial phasic and tonic contractions to 0.1 microM angiotensin II (AII). A phenylephrine (PE) concentration-response curve was performed on carotid arteries, and threshold values were determined. All WKY groups showed lower systolic blood pressure (131 +/- 4 mmHg) and reduced phasic AII induced contraction (7.4 +/- 4.7%) compared with SHRSP (217 +/- 4 mmHg; 37.2 +/- 4%). Antihypertensive treatment reduced blood pressure (ramipril: 168 +/- 2; hydral/HCTZ: 198 +/- 6 mmHg) but not phasic AII responses in adult SHRSP; adult WKY rats were unaffected by treatment. Threshold values for PE in carotid arteries were lower in SHRSP than in WKY, indicating increased sensitivity. However, SHRSP treated with ramipril did not demonstrate increased sensitivity to PE. These data support the hypothesis that blood pressure and sensitivity to PE but not contractile responsiveness to AII in adult SHRSP are determined by an AII-sensitive mechanism during development.
Traub
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Department of Physiology, University of Michigan, Ann Arbor 48109-0622, USA.
Lloyd
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MC
Webb
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D000375:Aging / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D000818:Animals; D000959:Antihypertensive Agents / Q000008:administration & dosage / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D006830:Hydralazine / Q000008:administration & dosage / Q000494:pharmacology; D006852:Hydrochlorothiazide / Q000008:administration & dosage / Q000494:pharmacology; D006973:Hypertension / Q000188:drug therapy*; D016014:Linear Models; D009119:Muscle Contraction / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D017257:Ramipril / Q000008:administration & dosage / Q000494:pharmacology; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D006852:Hydrochlorothiazide; D000804:Angiotensin II; D006830:Hydralazine; D017257:Ramipril