Impairment of neurally-mediated vasoconstriction in DOCA-salt hypertensive dogs.

Several biochemical studies indicate that hypertension produced by administration of deoxycorticosterone acetate (DOCA) plus saline as the drinking fluid is accompanied by significant increases in catecholamine turnover rates and a decrease in catecholamine content of peripheral tissues. In the present study the functional significance of such biochemical changes was assessed by evaluating vasoconstrictor responsiveness to neurogenic and humoral interventions in DOCA-salt hypertensive dogs. Administration of DOCA, 5 mg/kg subcutaneously twice a week for four weeks to unilaterally nephrectomized dogs given drinking fluid containing 1% sodium chloride produced a significant increase in blood pressure within one week. At the end of 4 week treatment period, the animals were anesthetized with pentobarbital (35 mg/kg) and sympathetic neurotransmission to the hindlimb and kidney was evaluated. Femoral as well as renal vasoconstrictor responses to sympathetic nerve stimulation were significantly inhibited in the hypertensive group in comparison with control animals. Vasoconstriction elicited by exogenous norepinephrine in both these vasculatures was similar in control and hypertensive groups. Femoral vasodilator responses to adenosine, bradykinin and PGE2 were significantly attenuated in the hypertensive group. While indomethacin (10 mg/kg) did not significantly affect renal vasoconstrictor responses to renal nerve stimulation in both the groups of animals, it caused a significant increase in the blood pressure of hypertensive group but not of control group. These results do not support the hypothesis of an increase in neurogenic function contributing to DOCA-salt hypertension. It is suggested that a reduction in sympathetic neurogenic influence may serve to protect against the rise in blood pressure during DOCA-salt administration.