Diltiazem maintains renal vasodilation without hyperfiltration in hypertension: studies in essential hypertension man and the spontaneously hypertensive rat.
The systemic and renal hemodynamic effects of diltiazem were determined in patients with mild to moderately severe essential hypertension and in rats with spontaneous hypertension (SHR). Seven patients were treated for one full year (300 mg/day, average dose) and 10 SHR and 10 normotensive Wistar-Kyoto (WKY) rats received 1 and 2 mg/kg, intravenously. In both man and rat with genetic hypertension, arterial pressure was reduced through a fall in total peripheral resistance without associated reflexive increases in heart rate and cardiac index; and the patients demonstrated no change in plasma volume. In both man and the SHR: renal blood flow increased (in SHR not statistically significant) as arterial pressure and renal vascular resistance fell; glomerular filtration rate (GFR) remained unchanged and the filtration fraction (FF) significantly fell; and calculated intrarenal hemodynamic indices (using the Gomez formulae) demonstrated falls in afferent and efferent glomerular arteriolar pressures and resistances and in intraglomerular pressures, thereby explaining the unchanged GFRs and the decline in FF. These findings in both hypertensive man and rat are in contrast with those of the normotensive WKY that only demonstrated a fall in afferent glomerular arteriolar resistance. Thus, these data demonstrate that diltiazem controlled arterial pressure in both forms of genetic hypertension associated with falls in systemic and renal arteriolar resistances and with improved intrarenal hemodynamics without glomerular hyperfiltration.
Isshiki
T
T
Research Division, Alton Ochsner Medical Foundation, New Orleans, Louisiana 70121.
Amodeo
C
C
Messerli
F H
FH
Pegram
B L
BL
Frohlich
E D
ED
D000328:Adult; D000368:Aged; D000803:Angiotensin I / Q000097:blood; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004110:Diltiazem / Q000494:pharmacology* / Q000627:therapeutic use; D005260:Female; D005919:Glomerular Filtration Rate / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects; D006801:Humans; D006973:Hypertension / Q000188:drug therapy / Q000503:physiopathology*; D007668:Kidney / Q000098:blood supply* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D051381:Rats; D011918:Rats, Inbred SHR; D011921:Rats, Inbred WKY; D012039:Regional Blood Flow / Q000187:drug effects; D012079:Renal Circulation / Q000187:drug effects*; D013152:Splanchnic Circulation / Q000187:drug effects; D014655:Vascular Resistance / Q000187:drug effects; D014664:Vasodilation / Q000187:drug effects
D000803:Angiotensin I; D004110:Diltiazem