Abstract
Nitric oxide (NO) is a tonically produced vasodilator that maintains blood pressure (BP) in the normal animal. In these studies, we produced chronic NO blockade by oral administration of the NO synthesis inhibitor nitro-L-arginine methyl ester (L-NAME), which produced sustained hypertension and increased renal vascular resistance (RVR) in conscious rats. Acute blockade of the angiotensin II type 1 (AT1) receptor with losartan had little effect on BP and RVR in either chronically NO-blocked or normal conscious rats. Acute blockade of the alpha 1-adrenoceptor with prazosin produced moderate similar falls in BP in both chronically NO-blocked and normal rats. The combination of AT1 and alpha 1-adrenoceptor blockade was profoundly antihypertensive and was particularly effective in lowering BP in chronically NO-blocked rats where the hypertension was obliterated. In contrast, the increased RVR persisted in chronically NO-blocked rats receiving combined acute AT1 and alpha 1-adrenoceptor blockade. These observations indicate that, in the sustained phase of chronic NO blockade, the hypertension is largely due to the combined activities of alpha 1-adrenoceptor and AT1 stimulation.
Publication types
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Administration, Oral
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Angiotensin II / physiology*
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Angiotensin Receptor Antagonists*
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Animals
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Arginine / administration & dosage
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Arginine / analogs & derivatives*
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Arginine / pharmacology
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Biphenyl Compounds / pharmacology*
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Blood Pressure / drug effects
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Glomerular Filtration Rate / drug effects
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Hematocrit
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Hypertension / chemically induced
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Hypertension / physiopathology*
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Imidazoles / pharmacology*
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Kidney / blood supply
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Kidney / physiology
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Kidney / physiopathology*
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Losartan
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Male
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NG-Nitroarginine Methyl Ester
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Nitric Oxide / antagonists & inhibitors*
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Prazosin / pharmacology*
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Rats
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Rats, Sprague-Dawley
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Receptors, Adrenergic, alpha-1 / drug effects
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Receptors, Adrenergic, alpha-1 / physiology*
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Receptors, Angiotensin / physiology
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Reference Values
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Regional Blood Flow / drug effects
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Renal Circulation / drug effects
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Renal Circulation / physiology*
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Tetrazoles / pharmacology*
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Vascular Resistance / drug effects
Substances
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Angiotensin Receptor Antagonists
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Biphenyl Compounds
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Imidazoles
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Receptors, Adrenergic, alpha-1
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Receptors, Angiotensin
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Tetrazoles
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Angiotensin II
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Nitric Oxide
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Arginine
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Losartan
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NG-Nitroarginine Methyl Ester
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Prazosin