Control of Hindlimb Vascular Resistance and Vascular Responsiveness in Doca-Salt Hypertensive Dogs

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Abstract
Administration of deoxycorticosterone acetate (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 the 4 week treatment period, the animals were anesthetized with pentobarbital (35 mg/kg), and the right hindlimb was perfused with controlled blood flow using a Sigmamotor pump. Pressure flow curves obtained in the perfused hindlimb vasculature were similar before and after sympathetic denervation in both the normotensive and the hypertensive animals suggesting that the overall hindlimb vascular resistance (HVR) as well as the neurogenic contribution to the maintenance of HVR was not altered in the hypertensive animals. Phentolamine produced a significantly larger decrease in the HVR of the hypertensive animals implicating a greater contribution by the circulating catecholamines to the maintenance of HVR in these animals. Administration of hydralazine directly into the limb produced larger decreases in the HVR of normotensive dogs in comparison with the hypertensive group. Hindlimb vasoconstrictor responses to norepinephrine and angiotensin were significantly potentiated, whereas the vasodilator responses to acetylcholine and histamine were significantly attenuated in the hypertensive group. Similarly, while systemic pressor responses to phenylephrine and angiotensin were potentiated, depressor responses to histamine and bradykinin were significantly attenuated in the hypertensive animals. Furthermore, reflex vasodilation in response to phenylephrine and angiotensin was also inhibited in the hypertensive dogs. These results suggest that an increase in circulating catecholamines, increased vasoconstrictor responsiveness and a decrease in the ability of the vascular smooth muscle to relax may contribute to the development and/or maintenance of DOCA-salt hypertension in the dog.

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