Hydrochlorothiazide Increases Efferent Glomerular Arteriolar Resistance in Spontaneously Hypertensive Rats

Background: Micropuncture studies were performed to determine the intrarenal hemody namic effects of two conventional antihypertensive agents, hydrochlorothiazide (HCTZ) and hydralazine (HYDR) alone and in combination.

Methods and Results: Male spontaneously hypertensive and normotensive Wistar Kyoto rats (19 weeks old) were treated for 3 weeks with vehicle (control), HCTZ (80 mg/kg/d), HYDR (5 mg/kg/d), or combined therapy (HCTZ 30 mg/kg/d and HYDR 2 mg/kg/d). Each treatment significantly reduced arterial pressure while effective renal plasma flow, glomerular filtration rate and single nephron glomerular filtration rate were unaffected by any treatment in either strain. In spontaneously hypertensive rats HCTZ decreased single nephron plasma flow (11 ± 8 to 84 ± 4 nL/min; P < .05) but, despite this reduction, glomerular pressure remained unchanged (51.4 ± 0.7 to 52.1 ± 0.8 mmHg) attributable to increased efferent glomerular resistance (1.58 ± 0.14 to 2.11 ± 0.12 10 U; P < .05). By contrast, HYDR increased single nephron plasma flow (to 147 ± 8 nL/min; P < .01) and decreased efferent glomerular resis tance (to 1.09 ± 0.09 U; P < .05). Combined treatment produced responses similar to HCTZ when used alone, thereby nullifying the beneficial efferent glomerular resistance effects: sin gle nephron plasma flow ± fell (to 89 ± 7 nL/min; P < .05) and efferent glomerular resistance increased (to 2:05 ± 0.17 U; P < .05). In Wistar Kyoto rats, HCTZ and combined treatment had no-effect. HCTZ alone induced glomerular ischemia that was associated with efferent glomerular arteriolar constriction in these spontaneously hypertensive rats.

Conclusions: These findings provide a possible explanation for the lack of improved renal target-organ damage in controlled multicenter trials employing thiazide diuretics.