Preliminary observations of the acute effects of selective serum thromboxane inhibition and angiotensin converting enzyme inhibition on blood pressure and renal hemodynamics in hypertensive humans

J Clin Pharmacol. 1989 Dec;29(12):1108-16. doi: 10.1002/j.1552-4604.1989.tb03287.x.

Abstract

CGS 13080, a selective thromboxane synthetase inhibitor, was given intravenously (0.6 mg/kg over 6 hours) to eight hypertensive (diastolic 95-115 mm Hg) euvolemic caucasian females on their customary salt intake (24 hour urine Na: 142.9 +/- 14.8 meq). No change occurred in blood pressure or glomerular filtration rate (GFR): 95.2 +/- 7.2, control versus 95.0 +/- 9.0, CGS 13080 (ml/min); or renal plasma flow (RPF): 363.2 +/- 34.2, control, versus 373.2 +/- 31.2, CGS 13080, (ml/min). Prostaglandin production was altered: platelet generation of thromboxane B2 83.3 +/- 10.9, control, versus 5.4 +/- 1.8, CGS 13080 (ng/hr) (P less than .001); urinary prostaglandin E (PGE) 249.0 +/- 56.3, control, versus 443.9 +/- 79.8, CGS 13080 (ng/6 hr) (P = .06); urinary 6-ketoprostaglandin F1 alpha (6-keto-PGF1 alpha) 188.6 +/- 23.4, control, versus 287.9 +/- 21.8, CGS 13080 (ng/6 hr) (P = .01); urinary thromboxane B2 54.8 +/- 12.9, control, versus 58.6 +/- 20.3 CGS 13080 (ng/6 hr) (P = NS). Serum levels of renin, angiotensin II and aldosterone were not altered by CGS 13080. Captopril when dosed to lower diastolic blood pressure 5-7 mm Hg did not significantly affect GFR, RPF or RVR. Nor did it affect platelet generation of thromboxane B2 or urine concentrations of PGE, 6-keto-PGF1 alpha or thromboxane B2. Captopril did increase renin levels 1.2 +/- 0.2, control, versus 2.9 +/- 1.1, captopril (ng/ml/hr) (P = NS), but did not statistically change angiotensin II, or aldosterone levels.(ABSTRACT TRUNCATED AT 250 WORDS)

Publication types

  • Clinical Trial

MeSH terms

  • Adult
  • Aldosterone / blood
  • Aldosterone / urine
  • Angiotensin-Converting Enzyme Inhibitors / therapeutic use*
  • Blood Pressure / drug effects*
  • Captopril / therapeutic use*
  • Clinical Trials as Topic
  • Female
  • Hemodynamics / drug effects
  • Humans
  • Hypertension / drug therapy*
  • Hypertension / metabolism
  • Hypertension / physiopathology
  • Imidazoles / therapeutic use*
  • Kidney / drug effects*
  • Middle Aged
  • Potassium / urine
  • Prostaglandins / blood
  • Prostaglandins / urine
  • Pyridines / therapeutic use*
  • Renin-Angiotensin System / drug effects
  • Sodium / urine
  • Thromboxane B2 / biosynthesis*
  • Thromboxane-A Synthase / antagonists & inhibitors*

Substances

  • Angiotensin-Converting Enzyme Inhibitors
  • Imidazoles
  • Prostaglandins
  • Pyridines
  • Aldosterone
  • Thromboxane B2
  • Captopril
  • pirmagrel
  • Sodium
  • Thromboxane-A Synthase
  • Potassium