Enhanced 5-hydroxytryptamine release from vascular adrenergic nerves in spontaneously hypertensive rats

H Kawasaki, M Urabe, K Takasaki
1987 Hypertension  
The release of 5-hydroxytryptamine from the vascular adrenergic nerve by periarterial nerve stimulation in spontaneously hypertensive rats (SHR) was compared with that in normotensive Wistar-Kyoto rats (WKY). The isolated mesenteric vascular bed was perfused at a constant flow rate of 5 ml/min. Vasoconstrictor responses to periarterial nerve stimulation (4, 8, 12, and 16 Hz for 30 seconds) and 5-hydroxytryptamine (1 fiM), but not norepinephrine (1 nmol), were significantly greater in SHR than
more » ... WKY. After treatment with 5-hydroxytryptamine (1 fj.M) for 15 minutes, vasoconstrictor responses to periarterial nerve stimulation previously reduced by prazosin (50 nM) were restored and a frequency-dependent pressor response reappeared. However, 5-HT treatment did not significantly affect the pressor response to exogenously administered norepinephrine (1 nmol), which was previously inhibited by prazosin. The degree of the restoration in SHR was significantly greater than that in WKY at all frequencies used. The restoration of the pressor response to periarterial nerve stimulation after 5-hydroxytryptamine treatment did not occur in the presence of the selective 5-hydroxytryptamine 2 receptor antagonists ketanserin (10 nM) or LY53857 (10 nM). In the perfused mesenteric vascular bed of both WKY and SHR prelabeled with [ 3 H]5-hydroxytryptamine, periarterial nerve stimulation (4-16 Hz) evoked a frequency-dependent increase in tritium efflux that was abolished by Ca 2+ -free Krebs-Ringer solution or tetrodotoxin (100 nM) and treatment with 6hydroxydopamine. The tritium efflux evoked by periarterial nerve stimulation was significantly greater in SHR than in WKY at all frequencies used. These results suggest that the release of 5hydroxytryptamine from adrenergic nerve endings by periarterial nerve stimulation is enhanced in the mesenteric vascular bed of the SHR. (Hypertension 10: 321-327, 1987) KEY WORDS • 5-hydroxytryptamine • vascular adrenergic nerve • spontaneously hypertensive rats S PONTANEOUSLY hypertensive rats (SHR) have been used as a model for studying human essential hypertension. The increased total vascular resistance resulting from enhanced sympathetic adrenergic tone is postulated to be the cause of this hypertension. 1 However, actual mechanisms underlying the development and maintenance of the hypertension remain unresolved. Several lines of evidence suggest that 5-hydroxytryptamine (5-HT) may be involved in the hypertension of SHR. 2 In fact, the vasoconstrictor response to 5-HT has been shown to be Materials and Methods The study used 46 male SHR (14-15 weeks old) and 45 age-matched WKY (Charles River Japan, Atsugi, Japan), weighing 309.8 ± 2.1 and 294.9 ± 2.2 g, respectively. The animals were given food and water ad libitum and were housed in an air-conditioned room (20 ± 1°C) with a 12-hour light/dark cycle (light on at 0730). Blood Pressure Measurement The animals were anesthetized with pentobarbital Na (50 mg/kg i.p.). Before the operation, the left carotid artery was cannulated and mean arterial pressure was recorded on a polygraph (Model RM-6000; Nihon Kohden, Tokyo, Japan) with a pressure transducer (Model P23ID; Gould Statham Instruments, Hato Rey, Puerto Rico). Perfusion of the Mesenteric Vascular Bed The mesenteric vascular bed was prepared for perfusion by the method of McGregor, 14 as reported previously. 13 The isolated mesenteric vascular bed was placed on a 10-ml water-jacketed organ bath maintained at 37 °C and perfused with modified Krebs-Ringer bicarbonate solution at a constant flow rate of 5 ml/min by means of a peristaltic pump (Model SJ-1215; ATTO, Tokyo, Japan). The preparation was also superfused with the same solution at a rate of 0.5 ml/min to prevent drying. The Krebs-Ringer solution had the following composition (in mM): NaCl, 120; KC1, 5.0; CaCl 2 , 2.4; MgSO 4 , 1.2; NaHCO 3 , 25; KH 2 PO 4 , 1.2; disodium EDTA, 0.027; and dextrose, 11.0 (pH = 7.4). Calcium-free Krebs-Ringer solution was prepared by omission of CaCl 2 when required. The Krebs-Ringer solution was aerated with a mixture of 95% O 2 , 5% CO 2 before passage through a wanning coil maintained at 37°C. Changes in the perfusion pressure were measured with a pressure transducer (Model MPU-0.5A; Nihon Kohden) and recorded on a polygraph (Model RM-25; Nihon Kohden).
doi:10.1161/01.hyp.10.3.321 pmid:3623684 fatcat:xv7ovay5fbaa5ofcgxwpt22qje