Effects of hemorrhage on renal nerve activity and of subsequent opiate receptor blockade with naloxone were studied in conscious rabbits. Mean arterial pressure remained constant at 77 ± 2 mm Hg through 17 ±2 ml/kg hemorrhage, while renal nerve activity increased by 159±16%. After 25 ± 1 ml/kg hemorrhage, mean arterial pressure fell by 42 ± 3 mm Hg, and renal nerve activity decreased below the prehemorrhagic control level by 41 ±15%. Bolus injection of naloxone (3 mg/kg i.v.) increased mean arterial pressure to 79 ±2 mm Hg, not significantly different from the prehemorrhagic control level. Renal nerve activity increased by 171 ±28%, comparable to the peak increase during nonhypotensive hemorrhage. On a different day, hemorrhage was repeated, and phenylephrine was infused during the subsequent hypotension. Phenylephrine increased mean arterial pressure to the prehemorrhagic control level. With increasing mean arterial pressure, renal nerve activity increased from its level during hypotensive hemorrhage and recovered toward the prehemorrhagic control level ( -26±11%), but it did not return to the peak value reached during nonhypotensive hemorrhage. To further examine the blocking effects of naloxone on changes in mean arterial pressure and renal nerve activity induced by exogenous opiate peptides, methionine-enkephalin was injected both in the control state and after treatment with naloxone. A bolus injection of methionine-enkephalin (10 fig/kg) decreased mean arterial pressure ( -8.1 ±2.0 mm Hg) and renal nerve activity ( -95 ± 1%). Pretreatment with naloxone (0.5 mg/kg) effectively blocked this depressor effect and reduction in renal nerve activity. These results indicate that hi conscious rabbits, hemorrhage elicits a biphasic effect on renal nerve activity that rises initially during nonhypotensive hemorrhage and then falls during hypotensive hemorrhage. This decrease in renal nerve activity is reversed by naloxone. Therefore, one mechanism by which renal nerve activity decreases during hypotensive hemorrhage appears to involve opiate receptors.

Responses of renal nerve activity (RNA) to intravenous infusion of brain natriuretic peptide (BNP) were examined in chronically instrumented conscious rabbits with all baroreflexes intact, sinoaortic baroreceptor denervation (SAD), and SAD plus vagotomy. In intact rabbits, an infusion of BNP at a rate of 0.3 microgram.kg-1.min-1 for 30 min decreased mean arterial pressure (MAP) by 8 +/- 1 mmHg and increased RNA by 48 +/- 4% but did not alter heart rate (HR). The decrease in MAP in SAD rabbits (20 +/- 3 mmHg) was greater than in intact rabbits, whereas RNA increased less (21 +/- 7%). After SAD plus vagotomy, BNP lowered MAP by 25 +/- 4 mmHg, whereas RNA was not altered significantly. To further examine the effects of BNP on baroreflex control of HR and RNA, the baroreceptors were stimulated or unloaded by raising or lowering MAP by injections of phenylephrine or glyceryl trinitrate, respectively. The maximum change in each HR or RNA response to phenylephrine or glyceryl trinitrate was plotted against the maximum change in each MAP response and a logistic function curve was fitted to the MAP-HR and MAP-RNA relationship. BNP did not alter the slope of either curve but shifted both curves to the left. These results indicate that 1) in intact rabbits, BNP increases RNA due to sinoaortic and cardiopulmonary baroreflexes and 2) BNP resets the baroreflex control of HR and RNA to a lower arterial pressure.

The baroreflex control of heart rate and renal nerve activity were examined in conscious Watanabe heritable hyperlipidaemic (WHHL) rabbits. Normal Japanese white rabbits were used as controls. The concentrations of serum cholesterol and triglyceride in WHHL rabbits were ten times higher than those in normal rabbits. The basal values of mean arterial pressure, pulse pressure and heart rate in WHHL rabbits were significantly higher than those in normal rabbits. Baroreceptors were stimulated or unloaded by raising or lowering arterial pressure with injections of phenylephrine or glyceryl trinitrate respectively. The peak changes in heart rate and renal nerve activity were plotted against the peak changes in mean arterial pressure, and a logistic function curve was fitted to the relationships between mean arterial pressure and heart rate, or mean arterial pressure and renal nerve activity. The slopes of both heart rate and renal nerve activity declined in WHHL rabbits. The response of renal nerve activity to acute volume expansion (10 ml.kg-1) with isotonic iso-oncotic dextran was further examined. In the normal rabbit, volume expansion caused renal nerve activity to decrease by 60 +/- 5%, while mean arterial pressure did not change. In the WHHL rabbit the decrease in renal nerve activity caused by volume expansion was significantly attenuated (42 +/- 3%). These results indicate that both sino-aortic and cardiopulmonary baroreceptor mediated changes in renal nerve activity were impaired in the WHHL rabbit.

Changes in sensitivity of the rapidly acting arterial pressure control (AP) system with aging were investigated. Two catheters, one for pressure measurement and the other for inducing hemorrhage from the aorta, were chronically implanted in 25 rabbits from the same colony (aged 6 to 30 months). A few days after the operations, each animal was quickly bled (2 ml/kg body weight) while it was conscious. The hemorrhage experiment was repeated 16 times and the mean arterial pressure responses were sampled with an A/D-converter and stored in a digital computer, the 16 strings of data being pooled for each animal. The overall open-loop gain (G) of the AP-system was estimated from the individually pooled responses. In the present study, aging exerted no significant effect on the value of G (7.1) as evaluated by KruskalWallis' non-parametric one criterion variance analysis (p>0.05).The reflex sensitivity of the AP-system over the pressure ranges used in this experiment thus appears to be unaffected by aging over the range from 6 to 30 months.

1. We examined whether or not circulating alpha-agonist modified baroreflex vasoconstriction of the hindlimb, using anaesthetized dogs in which the limb was vascularly isolated and perfused with blood from a donor dog using a pulsatile pump.2. The open-loop gain (G) of the baroreflex was estimated from changes in mean arterial pressure following mild quick haemorrhage from the aorta of the recipient dog.3. The hindlimb perfusion pressure increased after haemorrhage due to neurogenic vasoconstriction.4. An overall gain (Gh) ofthe baroreflex hindlimb vascular bed control system was estimated from the ratio of the increase in hindlimb perfusion pressure to the change in systemic arterial pressure of the recipient dog.5. Administration of a relatively selective al-agonist with no prejunctional p2 stimulating action (phenylephrine) or a selective a2-agonist (clonidine) to the donor dog increased its systemic arterial pressure and augmented Gh.6. Since both drugs were administered to the donor dog and could not enter into the recipient dog, these drugs did not affect the recipient's sympathetic nervous system, including the central nervous system and afferent limb of the baroreflex system. Therefore, these drugs could modify baroreflex vasoconstriction of the hindlimb only at the junction of the efferent sympathetic nerve and the vascular smooth muscle.7. It was concluded that postjunctional a-adrenoceptor stimulation augments neurogenic vasoconstriction.