Rostral ventrolateral medulla as a site for the central hypertensive action of kinins

Abstract

In the present study, we focused on the rostral ventrolateral medulla as a possible site of action for kinins because of its established importance in the central regulation of the cardiovascular system. Unilateral microinjections of 100 pmol to 4 nmol bradykinin into the rostral ventrolateral medulla produced dose-dependent increases in mean arterial pressure in Sprague-Dawley (SD) rats, Wistar-Kyoto (WKY) rats, and spontaneously hypertensive rats (SHR). The dose-response curves for the hypertensive responses to bradykinin in SD and WKY rats were essentially the same, whereas the hypertensive effect of bradykinin was significantly greater in SHR than in either SD or WKY rats. The kinin B2 receptor antagonists D- Arg0,Hyp3,Thi5.8,D-Phe7-bradykinin and Hoc 140 inhibited the hypertensive responses to bradykinin in both SHR and WKY rats. The hypertensive effect of 500 pmol bradykinin was reduced 65±5% after 4 nmol of D-Arg0,Hyp3,Thi5.8,D-Phe7-bradykinin in SHR and 50±16% in WKY rats, whereas 1 nmol Hoe 140 abolished the hypertensive effect of 500 pmol bradykinin injected into the rostral ventrolateral medulla. Microinjection of D-Arg0,Hyp3,Thi5.8,D-Phe7-bradykinin produced prolonged dose-dependent decreases in mean arterial pressure and heart rate. Blood pressure decreased 70±8 mm Hg and heart rate decreased 49±9 beats per minute in SHR, whereas in WKY rats mean arterial pressure decreased 12±4 mm Hg, with no change in heart rate. In a similar fashion, Hoe 140 caused a 51±7 and 17±3 mm Hg reduction in blood pressure in SHR and WKY rats, respectively. Collectively, these results suggest that a hyperactive kallikrein-kinin system in this region of the brain may be involved in the maintenance of blood pressure in the SHR model.