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The role of sympathetic function in the mechanism of the decrease in arterial pressure that follows withdrawal of an intravenous infusion of arginine vasopressin (AVP) in spontaneously hypertensive rats (SHR) was studied by comparing this withdrawal-induced antihypertensive phenomenon (WAP) in rats with intact sympathetic function to those subjected to sympathectomy. Sympathectomy with guanethidine did not lower blood pressure significantly in either SHR or normotensive Wistar-Kyoto (WKY) rats despite a marked impairment of sympathetic function as judged by a dramatic attenuation of blood pressure responses to tyramine and by evidence of denervation supersensitivity to phenylephrine. Cessation of a 3-h intravenous infusion of AVP (20 ng.kg-1.min-1) was associated with large and prolonged decrease in pressure below preinfusion levels in SHR with intact sympathetic function: 5 h after stopping the infusion, pressure was 27 +/- 3 mmHg below preinfusion levels. In sympathectomized SHR, the decrease in pressure after cessation of the AVP infusion was much larger: 5 h after the infusion, pressure was 44 +/- 2 mmHg below preinfusion levels. In contrast to SHR, pressure returned to control levels in WKY with intact sympathetic function after withdrawal of AVP. A small but significant decrease in pressure occurred after withdrawal of AVP in sympathectomized WKY. The results are consistent with the hypothesis that withdrawal of sympathetic activity is a contributing factor or a prerequisite condition for development of a WAP.

Mean arterial pressure (mmHg (1 mmHg = 133.322 Pa)), sodium excretion rate (mumol.kg-1.min-1), and urine flow (microL.kg-1.min-1) were measured in conscious unrestrained spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) before, during, and after a 3-h intravenous infusion of arginine vasopressin (20 ng.kg-1.min-1), an equipressor dose of phenylephrine, or an infusion of the vehicle. Cessation of the phenylephrine infusion was associated with a return of arterial pressure to preinfusion control values in both SHR and WKY. Cessation of the vasopressin infusion was also associated with a return of arterial pressure to preinfusion values in WKY. In contrast, in the SHR, arterial pressure fell from a preinfusion control level of 164 +/- 6.2 to 137 +/- 4 mmHg within 1 h of stopping the vasopressin infusion. Five hours after stopping the infusion, pressure was 134 +/- 3 mmHg (29 +/- 5 mmHg below preinfusion levels). Similar to the WKY, cessation of a vasopressin infusion was associated with a return of arterial pressure to preinfusion values in Sprague-Dawley rats. Thus, the failure to observe a hypotensive response in normotensive rats was not a peculiarity of the WKY strain. Sodium excretion rates increased during the infusions of vasopressin to a greater extent in SHR than in WKY. However, the natriuresis induced by phenylephrine was not significantly different from that generated by vasopressin in SHR, and in WKY, the natriuresis was greater for phenylephrine than for vasopressin. Urine output increased to a greater extent during the infusions of phenylephrine in both SHR and WKY than during vasopressin infusion.(ABSTRACT TRUNCATED AT 250 WORDS)

The importance of the autonomic nervous system (ANS) in the withdrawal-induced antihypertensive phenomenon (WAP) to arginine-vasopressin (AVP) in the spontaneously hypertensive rat (SHR) was investigated by studying the response to AVP infusion and withdrawal in the presence and absence of ganglionic blockade. In the absence of autonomic blockade, AVP infusion (20 ng/kg/min for 3 h) produced similar pressor responses initially in the SHR (45 +/- 2.0 mm Hg) and in the Wistar-Kyoto rat (WKY) (43 +/- 3.3 mm Hg). The pressor response was not well-maintained in SHR, falling to 21 +/- 0.8 mm Hg above preinfusion basal values by the end of the 3-h infusion. Cessation of the infusion was associated with a dramatic decrease in pressure below basal levels in the SHR: 3 h after the withdrawal of AVP, pressure had dropped from the preinfusion level of 171 +/- 4.0 mm Hg to 141 +/- 4.5 mm Hg, whereas pressure had returned to control levels in the WKY. In the presence of the ganglionic blocking agent, the changes in pressure both during and after the AVP infusion were similar in SHR and WKY: 3 h after the withdrawal of the AVP infusion, pressure was only slightly reduced below preinfusion levels in SHR (from 112 +/- 4.6 to 100 +/- 2.9 mm Hg) and WKY (from 76 +/- 2.7 to 75 +/- 2.6 mm Hg). The results suggest that an intact ANS is important to the expression of the WAP in the SHR, in that the WAP may require a withdrawal of sympathetic tone.

Arterial pressure and heart rate were recorded in three groups of conscious unrestrained rats before, during and after a three-hour intravenous infusion of arginine vasopressin (AVP; 20 ng/kg/min). Before infusion of AVP, basal arterial pressure was 152 +/- 3.2 mm Hg for the Doca-salt hypertensive group, 117 +/- 3.2 mm Hg for the uninephrectomized control group, and 111 +/- 2.1 mm Hg for the sham-operated control group. The changes in arterial pressure at each of the time points during the three-hour infusion of AVP were not significantly different among the three groups. Cessation of the AVP infusion was associated with a dramatic and prolonged fall of arterial pressure below preinfusion basal levels in the Doca-salt hypertensive group: pressure was 58 +/- 5.0 mm Hg below basal levels within 60 minutes of stopping the infusion and was still 45 +/- 5.6 mm Hg below four hours later. Pressure in this group was 107 +/- 5.7 mm Hg five hours after stopping the infusion. In contrast, the fall in pressure in the two control groups was small. Five hours after stopping the infusion, pressure was 108 +/- 2.3 mm Hg in the uninephrectomized group and 102 +/- 1.7 mm Hg in the sham-operated group. Thus, five hours after stopping the infusion, blood pressures among the three groups were not significantly different. The Doca-salt hypertensive group had been rendered normotensive.(ABSTRACT TRUNCATED AT 250 WORDS)

Pressor responses and heart rate responses were recorded in spontaneously hypertensive rats (SHR) and in Wistar-Kyoto (WKY) rats during intravenous infusions of arginine vasopressin and phenylephrine under two experimental situations, first when cardiovascular reflexes were impaired by pretreatment with a ganglionic blocking agent (pentolinium) and second, when reflexes remained intact. In rats with ganglia blocked, pressor responses of SHR to vasopressin or to phenylephrine were similar to those of WKY rats. In rats with intact reflexes, pressor responses of SHR to phenylephrine were also similar to those of WKY rats but, in contrast, pressor responses of SHR to vasopressin were enhanced. Heart rate fell much more for any given elevation of blood pressure in WKY rats than in SHR during infusions of vasopressin and phenylephrine, and the bradycardia associated with these pressor agents was largely abolished by pentolinium. The results are consistent with the hypothesis that baroreflexes buffer the pressor activity of vasopressin in the normotensive WKY rat and that an impairment of baroreflex activity in SHR contributes to the enhanced pressor activity of vasopressin in these rats.

In spontaneously hypertensive rats (SHR) and their normotensive Wistar-Kyoto controls (WKY), prolonged intravenous administration of angiotensin II (AII, 0.2 microgram X kg-1 X min-1 for 3h) resulted in similar increases in arterial blood pressure. Heart rate decreased in WKY and increased in SHR. At the end of the infusion, blood pressure dropped substantially in SHR, but not in WKY: at 5 h after AII withdrawal, blood pressure in SHR had fallen from a control value of 172 +/- 3.3 to 146 +/- 3.9 mmHg (p less than 0.01), whereas pressure in WKY had fallen from 116 +/- 3.0 to 107 +/- 4.2 mmHg (statistically non significant). Thus, pressure at 5 h after AII withdrawal was still substantially higher (p less than 0.01) in the SHR than in the WKY. The results demonstrate that the fall in blood pressure following withdrawal of a prolonged infusion of AII in SHR is much less than that reported to occur following withdrawal of a prolonged infusion of vasopressin (AVP) in SHR.