Background The relative contributions of increases in myocardial collagen, collagen cross-linking, and the ratio of type I to type III collagen to the stiff myocardium in hypertension were determined.

Methods and Results We compared the action of hydralazine (0.07 mmol · kg⁻¹ · d⁻¹) with that of captopril (0.22 mmol · kg⁻¹ · d⁻¹) on the left ventricular end-diastolic (LVED) myocardial stiffness constant, k (g · cm⁻²) and LV myocardial interstitial characteristics in spontaneously hypertensive rats (SHRs) and Wistar Kyoto (WKY) control rats. LVED k (SHR, 27.9±1; WKY, 19.5±1.2; P<.01), myocardial hydroxyproline concentrations (HPRO; μg/mg dry wt) (SHR, 4.19±0.16; WKY, 3.17±0.09; P<.001), and collagen type I/III ratios (SHR, 7.1±0.7; WKY, 2.1±0.2; P<.001) were increased, whereas the percentage of myocardial collagen extracted after cyanogen bromide digestion (an index of cross-linked collagen) was decreased (SHR, 17±3; WKY, 41±4; P<.001) in SHRs compared with WKY controls. Captopril therapy reduced LVED k, myocardial HPRO, collagen type I/III, and augmented collagen solubility (43±4) in SHRs to values similar to those measured in WKY controls. Hydralazine therapy, despite a favorable effect on LVED k in SHRs (20.±1.6, P<.01 compared with untreated SHRs), failed to influence either myocardial HPRO (4.18±0.18) or collagen type I/III (8±1) but did improve collagen solubility (31±2).

Conclusions An association between alterations in LVED k and collagen solubility but not between changes in LVED k and total collagen or phenotype ratios after antihypertensive therapy in SHRs suggests that myocardial stiffness in hypertension is the consequence of an enhanced myocardial collagen cross-linking rather than of an increase in total collagen or type I phenotype concentrations.