title: 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.
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)
authors.affiliation: Department of Medicine, University of Maryland Hospital, Baltimore 21201.
authors.forename: M R
authors.initials: MR
authors.lastname: Weir
authors.forename: D K
authors.initials: DK
authors.lastname: Klassen
authors.forename: N
authors.initials: N
authors.lastname: Hoover
authors.forename: F L
authors.initials: FL
authors.lastname: Douglas
mesh_terms: D000328:Adult; D000450:Aldosterone / Q000097:blood / Q000652:urine; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000627:therapeutic use*; D001794:Blood Pressure / Q000187:drug effects*; D002216:Captopril / Q000627:therapeutic use*; D002986:Clinical Trials as Topic; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D007093:Imidazoles / Q000627:therapeutic use*; D007668:Kidney / Q000187:drug effects*; D008875:Middle Aged; D011188:Potassium / Q000652:urine; D011453:Prostaglandins / Q000097:blood / Q000652:urine; D011725:Pyridines / Q000627:therapeutic use*; D012084:Renin-Angiotensin System / Q000187:drug effects; D012964:Sodium / Q000652:urine; D013929:Thromboxane B2 / Q000096:biosynthesis*; D013930:Thromboxane-A Synthase / Q000037:antagonists & inhibitors*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D007093:Imidazoles; D011453:Prostaglandins; D011725:Pyridines; D000450:Aldosterone; D013929:Thromboxane B2; D002216:Captopril; C037787:pirmagrel; D012964:Sodium; D013930:Thromboxane-A Synthase; D011188:Potassium