Enhanced vascular responsiveness to Bay K 8644 in mineralocorticoid- and N-nitro arginine-induced hypertension.
The present study evaluates the response to the L-type voltage gated calcium channel agonist Bay K 8644 in two forms of experimental hypertension (mineralocorticoid- and hypertension induced by the nitric oxide synthase inhibitor N omega-nitro-L-arginine (N-Nitro arginine)) and under conditions of acute stretch. These studies test the hypothesis that increased L-type calcium channel activity in vasculature is a hallmark or general characteristic of hypertension. Male Sprague-Dawley rats were made hypertensive by subcutaneous implantation of deoxycorticosterone acetate (200 mg/kg DOCA) and given normal or high salt water (1% NaCl + 0.2% KCl); other rats were made hypertensive by ingestion of N-Nitro arginine (2% in water). Systolic blood pressures (SBP) were taken by the standard tail cuff method. Following development of hypertension, rats were anesthetized, and aortae or mesenteric arteries were isolated for measurement of isometric contractile force. Cumulative concentration response curves to Bay K 8644 (10(-10) to 10(-6) M), KCl (6 to 100 mM), or phenylephrine (10(-10)-3 x 10(-7) M) were evaluated. Isolated mesenteric arteries from rats given both DOCA and salt were most sensitive to Bay K 8644 (SBP = 191 +/- 6 mmHg, -log EC50 = 7.78 +/- 0.13), followed by rats receiving high salt alone (SBP = 118 +/- 6 mmHg, -log EC50 = 7.30 +/- 0.17), DOCA alone (SBP = 152 +/- 2 mmHg, -log EC50 = 7.25 +/- 0.15), and finally normal sham rats (SBP = 111 +/- 5 mm Hg, -log EC50 > or = 6.80 +/- 0.10). These data indicate that both DOCA and salt intake can independently influence responsiveness to Bay K 8644.(ABSTRACT TRUNCATED AT 250 WORDS)
Watts
S W
SW
Department of Physiology, University of Michigan, Ann Arbor.
Finta
K M
KM
Lloyd
M C
MC
Storm
D S
DS
Webb
R C
RC
D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester / Q000494:pharmacology*; D000284:Administration, Oral; D000594:Amino Acid Oxidoreductases / Q000037:antagonists & inhibitors; D000818:Animals; D001013:Aorta, Thoracic / Q000187:drug effects; D001120:Arginine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology / Q000633:toxicity; D001794:Blood Pressure / Q000187:drug effects*; D015220:Calcium Channels / Q000187:drug effects* / Q000502:physiology; D003900:Desoxycorticosterone / Q000008:administration & dosage / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004343:Drug Implants; D006973:Hypertension / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D017538:Mesenteric Artery, Superior / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D009569:Nitric Oxide / Q000096:biosynthesis / Q000502:physiology; D019001:Nitric Oxide Synthase; D019335:Nitroarginine; D010656:Phenylephrine / Q000494:pharmacology; D011189:Potassium Chloride / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D017673:Sodium Chloride, Dietary / Q000008:administration & dosage / Q000633:toxicity*; D013314:Stress, Mechanical; D014661:Vasoconstriction / Q000187:drug effects*
D015220:Calcium Channels; D004343:Drug Implants; D017673:Sodium Chloride, Dietary; D010656:Phenylephrine; D019335:Nitroarginine; D009569:Nitric Oxide; D003900:Desoxycorticosterone; D011189:Potassium Chloride; D001498:3-Pyridinecarboxylic acid, 1,4-dihydro-2,6-dimethyl-5-nitro-4-(2-(trifluoromethyl)phenyl)-, Methyl ester; D001120:Arginine; D019001:Nitric Oxide Synthase; D000594:Amino Acid Oxidoreductases