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

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 B 2 83.3 ± 10.9, control, versus 5.4 ± 1.8, CGS 13080 (ng/hr) ( P < .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 F 1a (6‐ketoPGF 1a ) 188.6 ± 23.4, control, versus 287.9 ± 21.8, CGS 13080 (ng/6 hr) (P = .01); urinary thromboxane B 2 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 B 2 or urine concentrations of PGE, 6‐keto‐PGF 1a or thromboxane B 2 . 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. To see if the angiotensin converting enzyme inhibitor, captopril, would unmask a hypotensive effect of CGS 13080, the same experiments were repeated with captopril being dosed for 2 weeks prior to treatment with CGS 13080. The blood pressure decrease seen with captopril was not augmented by CGS 13080. The two drugs when dosed together did not affect GFR or RPF, nor did they significantly affect urinary prostaglandin excretion. Our preliminary observations suggest that CGS 13080 as acutely dosed in this study inhibited serum thromboxane A 2 production and increased vasodilator prostaglandins breakdown products in the urine (PGE, 6‐ketoPGF 1a ), yet did not augment the hypotensive effect of captopril .