Hypotensive effect of urapidil: CNS site and relative contribution.

The purposes of our study were to determine the contribution of the CNS to the hypotensive effect of urapidil in the cat and the specific brain site of action of this agent. For the first purpose, urapidil was studied on preganglionic sympathetic nerve activity, arterial pressure, and heart rate. Three systemic bolus doses of urapidil were administered (0.22, 0.44, and 1.3 mg/kg). All three doses lowered arterial pressure, and the highest dose produced a significant decrease in sympathetic nerve discharge in five of six animals studied. The lower two doses had no significant effect on sympathetic activity, and none of the doses altered heart rate. These results suggest that a high i.v. dose of urapidil is required to evoke hypotension by an action in the central nervous system (CNS). For the second purpose, urapidil was applied bilaterally to the intermediate area of the ventral surface of the medulla in doses of 25 and 50 micrograms. These doses caused decreases in arterial pressure of -6.1 +/- 2.2 (p less than 0.05) and -21.0 +/- 5.9 (p less than 0.05) mm Hg, respectively, but no change in heart rate. In addition, respiratory stimulation also occurred with the higher dose as respiratory minute volume increased by 81 +/- 14 ml/min (p less than 0.05). The highest dose of urapidil had no effect on arterial pressure when applied to other chemosensitive areas of the ventral surface of the brain. Comparative studies with prazosin (10 micrograms applied bilaterally to the intermediate area) indicated no hypotensive effect of this alpha 1-adrenoceptor blocking agent.(ABSTRACT TRUNCATED AT 250 WORDS)

Maintenance of carotid baroreflex function in advanced age in the rat.

To evaluate the influence of age per se on the carotid sinus baroreceptors in the absence of hypertension and atherosclerosis, we employed the Fischer 344 rat model. In 14 adult (A, 6-9 mo) and 9 senescent (S, 24-26 mo) normotensive male Fischer 344 rats the left carotid sinus region was vascularly isolated with sinus nerve intact and perfused with oxygenated modified Kreb's solution. Simultaneous measurements of intrasinus pressure and femoral arterial pressure response were obtained during linear pressure increases (20-200 mmHg) in the vascularly isolated sinus. There was no age difference in base-line arterial pressure or heart rate. Both age groups demonstrated similar positive relations between basal femoral arterial pressure and the magnitude of the femoral pressure response to equivalent carotid sinus pressures. There were similar estimated sinus volumes at onset of systemic response (39 +/- 1, A; 39 +/- 1 microliter, S), time to initial systemic pressure response (9 +/- 1, A; 7 +/- 1 s, S), mean rates of femoral pressure decline (1.8 +/- 0.3, A; 2.1 +/- 0.3 mmHg/s, S), and return to base line (1.5 +/- 0.3, A; 1.4 +/- 0.3 mmHg/s, S) as well as magnitudes of systolic (25 +/- 3, A; 26 +/- 4 mmHg, S) and diastolic (21 +/- 2 A; 22 +/- 4 mmHg, S) pressure drops. Thus, in the Fischer 344 rat model of aging, which differs from the human in that it is not complicated by hypertension or atherosclerosis, carotid sinus baroreflex function appears to be well maintained in senescence.

Effect of electrical and chemical stimulation of the raphe obscurus on phrenic nerve activity in the cat.

The effect of electrical and chemical (L-glutamate) stimulation of the raphe obscurus on phrenic nerve activity was examined in the cat. Phrenic nerve activity was recorded from a C5 nerve root in anesthetized, paralyzed and artificially ventilated cats. Neural discharge was quantitated by integrating the phrenic nerve activity. The respiratory frequency was determined from the integrated nerve signal. Focal electrical stimulation (18-144 microA; 5-40 Hz; 100 microseconds pulse duration) resulted in significant (P less than 0.05) increases in both integrated phrenic nerve (IPN) amplitude and respiratory frequency. These changes were dependent upon current intensity and frequency of stimulation. The largest increases in IPN amplitude and respiratory frequency were 47 +/- 17% and 146 +/- 8%, respectively. To insure that the changes in integrated phrenic nerve activity (IPNA) were the result of stimulation of cell bodies and not axons of passage, L-glutamate (100, 200 nmol) was microinjected (100 nl) into the raphe obscurus. Significant (P less than 0.05) dose-related changes occurred in integrated phrenic nerve amplitude with an increase of 44 +/- 13% at 100 nmol and 80 +/- 13% at 200 nmol L-glutamate. No significant increase in respiratory frequency was observed with L-glutamate microinjection. The results suggest that the raphe obscurus may be involved in respiratory control.

Influence of age on cardiovascular reflex response in anesthetized rats.

To test the hypothesis that aging is associated with an altered hemodynamic response to physiological (nonpharmacological) stimuli, such as postural change and intravascular volume perturbations, we studied the adult (A, 6 mo) and senescent (S, 24 mo) Fischer 344 rat, a mammalian aging model not influenced by atherosclerosis or hypertension. Special emphasis was placed on the afferent limb of the baroreceptor reflex arc, an area not previously studied with respect to age. The base-line heart rate (HR), systemic arterial pressure (SAP), pulmonary arterial pressure (PAP), and carotid sinus nerve activity were not influenced by age. Following postural change (60 degrees upward tilt), the old animals demonstrated a greater drop in systolic pressure (-11 +/- 2, A; -21 +/- 4 mmHg, S; P less than 0.05), but there was no significant change in HR in either group. In response to a controlled withdrawal of 0.5 ml, the A had a greater reduction in systolic pressure (-29 +/- 4, A; -12 +/- 3 mmHg, S; P less than 0.01), whereas HR or PAP did not change; both groups showed a similar decrease in nerve activity. After infusions of 0.5 and 1.0 ml, the systolic and diastolic pressure changes were greater (P less than 0.02), and the changes in nerve activity appeared to be slightly more prolonged in the A compared with the S. Thus the response to changes in intravascular volume and posture are altered with age, and differences in volume-mediated venovasomotor reflex response may contribute to these age-related changes in the rat.