Induction of hypertension and cardiac hypertrophy in guinea pig by DOCA salt.

ABSTRACT

Experimental hypertension can be induced in rats by uninephrectomy, administration of deoxycorticosterone acetate (DOCA) and sodium chloride. We developed this model in the guinea pig, because it presents an isoenzymic myosin pattern and calcium-induced calcium release similar to those of humans. Unilateral nephrectomy was performed in 33 guinea pigs, after which they were given DOCA (300 mg/kg pellets, s.c.; n = 11, or 10 mg, i.m.; n = 12, 5 days a week for 5 weeks). One week after surgery, drinking water was supplemented with NaCl 9 g/l and KCl 2 g/l for 5 weeks. Control guinea pigs (n = 10) were nephrectomized but not treated. Five weeks after surgery, hemodynamic measurements were recorded and the animals sacrificed to assess the degree of left ventricular hypertrophy. Left ventricular hypertrophy was considered significant if the ratio of left ventricular weight/body weight was > 2.3 and if the thickness of the left ventricle free wall was > 3.5 mm. Results showed that the systolic, diastolic and mean blood pressures of the treated groups were 36% higher than in the control group. Cardiac hypertrophy occurred within 5 weeks, and resulted in an increase in left ventricle weight and in left ventricular hypertrophy. The possibility of using the DOCA salt model of experimental hypertension in the guinea pig could help to elucidate the mechanisms responsible for hypertension and induced left ventricular hypertrophy, and thus improve prevention and treatment.