An increased reactivity in hypertensive rats unaffected by prolonged antihypertensive therapy.

1. Isolated perfused mesenteric arteries obtained from chronic experimental hypertensive rats (deoxycorticosterone/NaCl) exhibited an increased reactivity to noradrenaline, 5-hydroxytryptamine and adenosine 5'-triphosphate (ATP) when compared with similar preparations from age-matched normotensive animals. 2. The dose-response curves to all three vasoconstrictor agents obtained from hypertensive animals exhibited a steeper slope, and higher maximum without any significant change in the threshold dose suggesting that adaptive/structural changes in the blood vessels had taken place. 3. Ten week treatments with antihypertensive combinations of hydrallazine, hydrochlorothiazide and reserpine or hydrallazine and mecamylamine lowered the systolic blood pressures of the hypertensive rats to those of normotensive animals and also reversed secondary changes such as periarteritis nodosa of the mesentery and cardiac hypertrophy. 4. The reactivity of these blood vessels to all these vasoconstrictor agents from the hypertensive rats with a normalized blood pressure was similar to those obtained with untreated hypertensive animals. 5. The persistent increased reactivity in the hypertensive rats after long-term anti-hypertensive treatment suggests that the hyperresponsiveness is secondary to the elevated blood pressures and that the adaptive/structural changes of the blood vessels in chronic hypertensive rats cannot be reversed by prolonged antihypertensive therapy.