Load versus humoral activation in the genesis of early hypertensive heart disease

Background-The role of load versus angiotensin Il (Ang II) and endothelin-l (ET) in the pathogenesis of hypertensive heart disease is controversial. W e sought to determine whether alterations in cardiac structure and function due to hypertension (HTN) were dependent on Ang II or ET activation. Methods and Results-Bilateral renal wrapping to produce HTN (n=12) or sham surgery (n=6) was performed in adult dogs, Weekly blood pressure, plasma re nin activity, Ang II, ET, and catecholamines were measured. Systolic tend-s ystolic elastance, Ees) and diastolic (tau) function were assessed in sham and HTN dogs at 5 (HTN-5wk) or 12 (HTN-12wk) weeks. Ang II and ET were assa yed in the left ventricle (LV) and kidney. Mean arterial pressure was highe r in renal wrap dogs at week 1 (*P <0.05 versus controls: 139 +/-4* versus 123 +/-4* mm Hg), week 5 (174 +/-7* versus 124 +/-4 mm Hg), and week 12 (18 1 +/- 12* versus 124 +/-4 mm Hg). LV mass index was increased in HTN-5wk (2 2%*) and HTN-12wk (39%*), LV fibrosis was increased in HTN-12wk. Ees was pr eserved in HTN-5wk and HTN-12wk. tau was increased in HTN-5wk (50 +/-3* ms) and HTN-12wk (62 +/- 10* ms) dogs compared with sham (41 +/-2 ms). Plasma Ang II, ET, catecholamines, and plasma renin activity were unchanged during the progressive HTN. Ang II and ET in LV and kidney were not different fro m controls. Conclusions-Systemic HTN induces LV hypertrophy, myocardial fibrosis, and i solated diastolic dysfunction in the absence of local or systemic activatio n of Ang II or ET. These findings suggest that load is the prevailing stimu lus for the structural and functional changes associated with early hyperte nsive heart disease.