Acute effects of a pseudo-tetrapeptide as renin inhibitor on blood pressure and renin-angiotensin system of sodium-repleted and sodium-depleted hypertensive patients.
The blood pressure and renin-angiotensin system effects of the new renin inhibitor, SR 43845 ([N-(pyridyl-3-propionyl)-phenylalanyl- histidyl-(3S,4S) ACHPA-isoleucylamino]-2-methyl-2-dihydroxy-1,3-propane), were studied in 12 hypertensive patients on a normal sodium intake who received a 30-min infusion of intravenous SR 43845 at one of 3 doses: 30, 100 or 300 micrograms/kg (4 patients per group). Eight further patients were infused with the 300 micrograms/kg dose 24 h after 80 mg furosemide orally. In sodium-repleted patients, the 30, 100 and 300 micrograms/kg doses induced a rapid fall in diastolic blood pressure (DBP) which culminated at 4.5, 7.5 and 3.9 mmHg, respectively. Salt depletion increased the renin inhibitor-induced fall in DBP to 10.8 mmHg. DBP was back to baseline at 60 min after starting the lowest dose and 180 min after starting the highest dose. Heart rate did not change. In four of the sodium-depleted patients, 50 mg captopril was given orally at T = 180 min, when blood pressure had returned to baseline. The decrease in BP (8.8 mmHg) was similar to that initially obtained with the renin inhibitor (10.1 mmHg). Plasma angiotensin (Ang) I was dose-dependently reduced by 62, 93 and 92% of baseline values 10 min after the start of the infusion in sodium-repleted patients, and by 90% in sodium-depleted patients; it returned to baseline in both situations between 180 and 360 min. Plasma Ang II levels changed in parallel with those of plasma Ang I.(ABSTRACT TRUNCATED AT 250 WORDS)
Inserm U367a, Paris, France.
T
T
Denolle
P
P
Luo
T T
TT
Guyene
C
C
Cazaubon
J
J
Sissmann
P
P
Corvol
J
J
Ménard
D000328:Adult; D001794:Blood Pressure / Q000187:drug effects*; D004151:Dipeptides / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D005260:Female; D005665:Furosemide / Q000627:therapeutic use; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D008297:Male; D008875:Middle Aged; D011674:Pulse / Q000187:drug effects; D012084:Renin-Angiotensin System / Q000187:drug effects*; D012964:Sodium / Q000172:deficiency / Q000502:physiology*; D000092502:Renin Inhibitors
D004151:Dipeptides; D005665:Furosemide; D012964:Sodium; D000092502:Renin Inhibitors; C060501:SR 43845