In vitro evidence for an inhibitory effect of atrial natriuretic peptide on vasopressin release.

The effect of Arg-atriopeptin III (ANP) on basal and stimulated (angiotensin II, acetylcholine and KCl depolarization) arginine vasopressin (AVP) release was characterized in the intact hypothalamo-neurohypophysial explant (HNS) and in isolated neurointermediate pituitary lobes (NIL). In initial experiments using 15-min incubation periods, ANP 10(-10) and 10(-9) M slightly inhibited basal AVP release in both NIL and HNS after a delay of at least 15 min. The most effective ANP concentration was 10(-10) M, and the inhibitory effect on AVP release was more marked in HNS (-52 +/- 5% of control compared to -29 +/- 8% for NIL). However, ANP 10(-10) M did not significantly attenuate KCl- or AII (10(-5) M)-stimulated AVP release from HNS after 15 min of exposure. When the incubation periods were increased to 30 min ANP 10(-10) and 10(-9) M significantly decreased AII-stimulated (10(-5) M) AVP release in a dose-dependent manner (p less than 0.05; p less than 0.01, respectively). The same concentrations of ANP did not significantly depress ACH-stimulated (10(-5) M) AVP release (p less than 0.1 for both concentrations). In summary, ANP generally inhibits AVP release in vitro by a slowly activated mechanism which appears to be specific for certain physiological stimuli. Although the site(s) of action cannot be absolutely localized to the ventral hypothalamus and/or the neurohypophysis, an effect in the hypothalamus seems very likely.

Baroreflex control of sympathetic outflow in pregnant rats: effects of captopril.

Arterial baroreflex control of renal sympathetic nerve activity (RSNA) was compared in nonpregnant (NP) and near-term pregnant (P) chloralose-anesthetized rats. Baroreflex curves were obtained by recording reflex changes in RSNA (expressed as a percent of base line) due to increases and decreases in mean arterial pressure (MAP) [intravenous phenylephrine and nitroprusside (NTP)]. The slope, midpoint (EP50), and threshold pressures of the baroreflex curves were compared. Base-line MAP was significantly lower in the pregnant animals (P = 96 +/- 3 vs. NP = 113 +/- 5 mmHg). The baroreflex curves of pregnant animals also had significantly lower threshold (P = 95 +/- 3 vs. NP = 110 +/- 5 mmHg) and midpoint values (P = 105 +/- 4 vs. NP = 119 +/- 5 mmHg). The response to unloading the baroreceptors was attenuated in the pregnant animals as indicated by a decrease in slope of the NTP portion of the baroreflex curve (P = 0.95 +/- 0.17 vs. NP = 1.61 +/- 0.29% nerve activity/mmHg). Responses to blockade of angiotensin-converting enzyme with captopril (2 mg/kg iv) were also examined. There were no differences in EP50 or slope among the control, captopril, and recovery baroreflex curves within either the nonpregnant or pregnant animals. However, after captopril, MAP decreased to a greater extent in the pregnant rats, yet RSNA increased to the same level for the two groups. Thus pregnancy results in a leftward shift of the baroreflex function curve toward a lower operating pressure range. In addition, pregnant rats demonstrated an impaired ability to increase sympathetic outflow above base-line values in response to a hypotensive challenge.

Converting enzyme inhibitors cause pressure-independent resetting of baroreflex control of sympathetic outflow.

The current study was performed to determine whether baroreflex resetting after acute administration of converting enzyme inhibitors (CEIs) was dependent on the concomitant decrease in mean arterial pressure (MAP). Reflex changes in lumbar sympathetic nerve activity (LSNA) due to increases and decreases in MAP [i.v. phenylephrine (PE) and nitroprusside infusions] were determined in normotensive and renal hypertensive (1-kidney, 1-clip) anesthetized WKY rats 1) before (control), 2) 15 min after intravenous captopril (2 mg/kg) or enalaprilat (300 micrograms), and 3) 15 min after MAP was returned to pre-CEI levels with intravenous PE. CEIs decreased MAP and caused a leftward shift of the MAP-LSNA curve toward a lower operating pressure range in all hypertensive and in one group of normotensive rats. The baroreflex curve remained shifted to the left even after MAP was restored to pre-CEI levels by infusion of PE. Thus CEIs cause a pressure-independent resetting of baroreflex control of sympathetic outflow within 15 min. This effect of CEIs is most likely due to elimination of a central nervous system effect of circulating angiotensin II and could contribute to the antihypertensive actions of this class of compounds.

Characterization of norepinephrine sensitivity in the maternal splanchnic circulation during pregnancy.

Vascular sensitivity to exogenous norepinephrine and transmural nerve stimulation was studied in the splanchnic bed of nonpregnant, early pregnant, and late pregnant rats. Resistance-size mesenteric arteries were removed from late pregnant (18 to 20 days), early pregnant (7 days), and nonpregnant cycling rats and mounted in a myograph system, which permits the precise setting of vessel circumference for the determination of norepinephrine sensitivity. Norepinephrine dose-response curves and frequency-response curves for transmural nerve stimulation were obtained in the presence and absence of cocaine, a specific inhibitor of neuronal reuptake. The mesenteric arteries of late pregnant rats were 1.5 times less sensitive to exogenous norepinephrine than arteries of both early pregnant and nonpregnant rats. Sensitivity to transmural nerve stimulation was decreased in both early and late pregnant rats compared with nonpregnant controls. Cocaine potentiated the response to both exogenous norepinephrine and transmural nerve stimulation in the pregnant rats so that responses between nonpregnant, early pregnant, and late pregnant rats were no longer different. This suggests a greater reuptake activity from pregnant rats. In conclusion, pregnancy is associated with a reduction in splanchnic norepinephrine sensitivity, which may be due partly to an increase in neuronal deactivation of norepinephrine. The maximum contractile response to norepinephrine also was decreased in late pregnancy, which suggests additional mechanisms for changes in norepinephrine vascular sensitivity.