Angiotensin-converting enzyme inhibition, but not calcium antagonism, improves a response of the renal vasculature to L-arginine in patients with essential hypertension.
Endothelial function has been shown to be impaired in patients with essential hypertension. The purpose of the present study was to determine whether antihypertensive drug therapy improves impaired endothelium-dependent renal vasorelaxation in essential hypertensive patients without atherosclerosis. We evaluated the effects of intravenous infusion of L-arginine (500 mg/kg given over 30 minutes) on systemic and renal hemodynamics in 27 patients with mild to moderate essential hypertension who were randomly assigned to treatment with either the angiotensin-converting enzyme inhibitor imidapril or the calcium antagonist amlodipine for 12 weeks in a double-blind fashion. After the 12 weeks, the decrease in blood pressure was similar in the imidapril (n=14) and amlodipine (n=13) groups. The increase in renal plasma flow was also similar in both groups. L-Arginine-induced renovascular relaxation was increased by imidapril (renal plasma flow, 9.6+/-5.1% to 14.4+/-7.4%; renal vascular resistance, -10.4+/-8.1% to -16.7+/-9.2%, P<0.05, respectively) but not by amlodipine. Urinary excretion of nitrite/nitrate in response to L-arginine was significantly increased by imidapril (90+/-29% to 134+/-63%, P<0.05) but remained unchanged by amlodipine. These findings suggest that angiotensin-converting enzyme inhibition improves the impaired endothelium-dependent renovascular relaxation in patients with essential hypertension due to the increase in nitric oxide production and that the reduction in blood pressure with a calcium antagonist does not play a major role in the potentiation of L-arginine/nitric oxide-mediated effects.
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan. yhigashi@mcai.med.hiroshima-u.ac.jp
Y
Y
Higashi
T
T
Oshima
S
S
Sasaki
Y
Y
Nakano
M
M
Kambe
H
H
Matsuura
G
G
Kajiyama
D000328:Adult; D000368:Aged; D017311:Amlodipine / Q000494:pharmacology* / Q000627:therapeutic use; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D000959:Antihypertensive Agents / Q000494:pharmacology* / Q000627:therapeutic use; D001120:Arginine / Q000008:administration & dosage / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology* / Q000627:therapeutic use; D003627:Data Interpretation, Statistical; D004311:Double-Blind Method; D004730:Endothelium, Vascular / Q000187:drug effects; D005260:Female; D006801:Humans; D006973:Hypertension / Q000188:drug therapy* / Q000503:physiopathology; D007093:Imidazoles / Q000494:pharmacology* / Q000627:therapeutic use; D048289:Imidazolidines; D007262:Infusions, Intravenous; D007668:Kidney / Q000098:blood supply / Q000187:drug effects*; D008297:Male; D008875:Middle Aged; D009566:Nitrates / Q000652:urine; D009569:Nitric Oxide / Q000502:physiology; D009573:Nitrites / Q000652:urine; D012079:Renal Circulation / Q000187:drug effects; D013997:Time Factors; D014655:Vascular Resistance / Q000187:drug effects
D000806:Angiotensin-Converting Enzyme Inhibitors; D000959:Antihypertensive Agents; D002121:Calcium Channel Blockers; D007093:Imidazoles; D048289:Imidazolidines; D009566:Nitrates; D009573:Nitrites; D017311:Amlodipine; D009569:Nitric Oxide; D001120:Arginine; C065166:imidapril