INDIRECT HYPERTENSIVE ACTIONS OF LONG-TERM INTRACAROTID ANGIOTENSIN-II INFUSION DURING OVINE PREGNANCY

Angiotensin II (AngII) influences the regulation of mean arterial pres sure (MAP) through numerous mechanisms, including an action of circula ting AngII on the brain to alter autonomic activity. We have obtained evidence that the relative importance of this effect is increased duri ng pregnancy. Consequently, these studies were undertaken to assess th e effects of bilateral infusion of AngII (0.35 ng . kg(-1) . min(-1) . artery(-1)) into the internal carotid arteries (ica) of sheep for 13 days. Six nonpregnant (NP) and six 105- to 125-day pregnant (PG) ewes were maintained in large metabolism cages, where MAP was continuously monitored. By day 10 of ica AngII infusion in NP ewes, MAP was increas ed from 83.9 +/- 1.6 to 92.9 +/- 2.8 mmHg (1 mmHg = 133.3 Pa) (p = 0.0 01). Twenty-four hour urine volume (UV, 2664 +/- 341 to 1583 +/- 228 m L; p = 0.005) and sodium excretion (U-Na V, 190 +/- 5 to 113 1 19 mmol /day; p = 0.005) were decreased. Cr-51-tagged blood volume (BV) was in creased on day 13 (3643 +/- 187 to 4379 +/- 446 mt; p = 0.05). In cont rast, by only day 6 of ica AngII infusion in PG ewes, MAP increased fr om 79.1 +/- 1.9 to 84.1 +/- 1.4 mmHg (p = 0.03) in association with a BV expansion from 3999 +/- 274 to 4207 +/- 275 mt. These changes were preceded by decreases in UV (2813 +/- 413 to 2198 +/- 362 mL; p = 0.01 ) and U-Na V (190 +/- 15 to 118 +/-: 26 mmol/day; p = 0.01). By day 13 , MAP had plateaued at 93.0 +/- 1.2 mmHg. There were no changes in pla sma AngII, plasma renin activity, arginine vasopressin, and atrial nat riuretic factor during ica AngII infusion in either NP or PG ewes, sug gesting that these effects are mediated via the central nervous system . Moreover, the data suggest that MAP is increased secondary to volume expansion associated with sodium and water retention. This effect app ears to be more readily exhibited during pregnancy. Furthermore, this study demonstrates the importance of the renin-angiotensin system in b lood pressure homeostasis by actions other than direct vasoconstrictio n.