ABSTRACT
BACKGROUND: To demonstrate reduced risk from reversing left ventricular hypertrophy (LVH) in hypertension, one must show that it is independent of blood pressure reduction. METHODS AND RESULTS: A feasibility study was conducted with 15 patients. The study employed 48-hour Holter recording, exercise treadmill (for ST-segment changes) and, as necessary, thallium scintigraphy and coronary angiography. All patients were treated for 3 months with quinapril (10 mg) and demonstrated decreased mean arterial pressure (125 +/- 3.1 vs 103 +/- 1.9 mmHg; P <.01) and left ventricular mass index (125 +/- 6.4 vs 104 +/- 4.9; P <.02) with preserved left ventricular function. There were no significant changes in these patients with moderate LVH in the incidence of arrhythmias; however, 4 of the 15 patients developed ST-segment changes prior to LVH reversal, and these changes did not recur in 3 patients following reversal of LVH or when pressure was allowed to rise. CONCLUSIONS: Ischemic changes, rather than development of arrhythmias, may be of greater value in demonstrating risk reduction with LVH reversal. Moreover, these preliminary data suggest pitfalls in demonstrating risk reduction after LVH reversal, indicating that more sensitive and adequate techniques are necessary to show risk reduction from LVH.
ABSTRACT
BACKGROUND: Micropuncture studies were performed to determine the intrarenal hemodynamic 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 (111 +/- 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 resistance (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: single 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.
