Angiotensin II and alpha 1-adrenergic tone in chronic nitric oxide blockade-induced hypertension.
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.
Qiu
C
C
Department of Physiology, West Virginia University, Morgantown 26506-9229.
Engels
K
K
Baylis
C
C
D000284:Administration, Oral; D000804:Angiotensin II / Q000502:physiology*; D057911:Angiotensin Receptor Antagonists; D000818:Animals; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D001713:Biphenyl Compounds / Q000494:pharmacology*; D001794:Blood Pressure / Q000187:drug effects; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006400:Hematocrit; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D007093:Imidazoles / Q000494:pharmacology*; D007668:Kidney / Q000098:blood supply / Q000502:physiology / Q000503:physiopathology*; D019808:Losartan; D008297:Male; D019331:NG-Nitroarginine Methyl Ester; D009569:Nitric Oxide / Q000037:antagonists & inhibitors*; D011224:Prazosin / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018340:Receptors, Adrenergic, alpha-1 / Q000187:drug effects / Q000502:physiology*; D011945:Receptors, Angiotensin / Q000502:physiology; D012016:Reference Values; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects / Q000502:physiology*; D013777:Tetrazoles / Q000494:pharmacology*; D014655:Vascular Resistance / Q000187:drug effects
D057911:Angiotensin Receptor Antagonists; D001713:Biphenyl Compounds; D007093:Imidazoles; D018340:Receptors, Adrenergic, alpha-1; D011945:Receptors, Angiotensin; D013777:Tetrazoles; D000804:Angiotensin II; D009569:Nitric Oxide; D001120:Arginine; D019808:Losartan; D019331:NG-Nitroarginine Methyl Ester; D011224:Prazosin