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We developed a chronic rat preparation in which a flow probe is placed around the ascending aorta and arterial catheters are implanted in the systemic and pulmonary circulations. This preparation was used to continuously monitor cardiac output (CO), systemic arterial pressure (Psa), and pulmonary arterial pressure (Ppa). More than 80% of the instrumented animals appeared healthy and continued to gain weight for longer than 2 wk. Stable CO, Psa, and Ppa were observed throughout this period. The effects of angiotensin II and hypoxia on the systemic and pulmonary circulations were studied, and possible adverse effects on the heart of long-term implantation of the flow probe were examined. This rat model provides a physiological small-animal preparation for short- and long-term hemodynamic and therapeutic studies on both the systemic and pulmonary circulations.

We have previously shown that iv glucagon improved survival in rats from 33 to 83% when given after, but not during, superior mesenteric artery (SMA) occlusion. This study investigated potential hemodynamic mechanisms of this effect. In Part 1, cardiac output (CO) was measured in 12 male Sprague-Dawley rats with an electromagnetic flow-probe that had been placed around the ascending aorta 5 days previously. Under pentobarbital anesthesia, the SMA was occluded for 85 min. All rats received normal saline (NS, 15 ml/kg/hr) for 1 hr before and after SMA declamping. Control rats (n = 6) received only NS. Treated rats (n = 6) received NS plus glucagon (1.6 micrograms/kg/min iv) for 1 hr postocclusion. CO decreased 50% during the first hour after SMA declamping in control rats, but only 11% in glucagon-treated rats (P less than 0.02). Systemic vascular resistance (SVR) increased by 90% in control rats by 1 hr after declamp, but only 9% in glucagon rats (P less than 0.04). Systemic blood pressure and heart rate were not different in the two groups. In Part 2, relative distribution of visceral blood flow was measured with radiolabeled microspheres injected in the aortic root before clamping, before declamping, and 1 hr postdeclamping in 10 rats (5 glucagon, 5 control) using the above protocol. After SMA clamping, the proportion of visceral blood flow distributed to the intestine fell from 45 to 20% (P less than 0.05). During reperfusion, the proportion of intestinal flow exceeded baseline (P less than 0.05), but was not different in control (64%) and glucagon-treated rats (56%).(ABSTRACT TRUNCATED AT 250 WORDS)

We studied the effects of synthetic atrial natriuretic factor (ANF, 28-amino acid peptide) on base-line perfusion pressures and pressor responses to hypoxia and angiotensin II (ANG II) in isolated rat lungs and on the following hemodynamic and renal parameters in awake, chronically instrumented rats: cardiac output (CO), systemic (Rsa) and pulmonary (Rpa) vascular resistances, ANG II- and hypoxia (10.5% O2)-induced changes in Rsa and Rpa, and urine output. Intra-arterial ANF injections lowered base-line perfusion pressures and blunted hypoxia- and ANG II-induced pressor responses in the isolated lungs. Bolus intravenous injection of ANF (10 micrograms/kg) into intact rats decreased CO and arterial blood pressures of both systemic and pulmonary circulations and increased Rsa. ANG II (0.4 micrograms/kg) increased both Rsa and Rpa, and hypoxia increased Rpa alone in the intact rats. ANF (10 micrograms/kg) inhibited both ANG II- and hypoxia-induced increases in Rpa but did not significantly affect the ANG II-induced increase in Rsa. The antagonistic effect of ANF on pulmonary vasoconstriction was reversible and dose-dependent. The threshold doses of ANF required to inhibit pulmonary vasoconstriction were in the same range as those required to elicit diuresis and natriuresis. The data demonstrate that ANF has a preferential relaxant effect on pulmonary vessels constricted by hypoxia or ANG II. Both the renal and the pulmonary vascular effects of ANF may represent fundamental physiological actions of ANF. These actions may serve as a negative feedback control system that protects the right ventricle from excessive mechanical loads.