ROLE OF ENDOGENOUS CENTRALLY RELEASED NO IN CARDIOVASCULAR ADAPTATIONTO HYPOVOLEMIA IN WKY AND SHR

The role of endogenous centrally released nitric oxide (NO) during hyp ovolemia was investigated in normotensive Wistar-Kyoto (WKY) and spont aneously hypertensive rats (SHR). Bleeding of the rats (1.3% of blood volume) was performed after intracerebroventricular (ICV) administrati on of: 1) artificial cerebrospinal fluid (series 1, time control, 8 WK Y and 8 SHR); 2) 0.5 mg N-G-nitro-L-arginine (L-NNA, 2.3 nmol), an inh ibitor of NO synthesis (series 2, 8 WKY and 7 SHR); and 3) 0.5 mg L-NN A followed by 1 mg (5.8 nmol) of L-arginine (L-Arg) (6 WKY and 5 SHR). In WKY, hypotension was associated with significant bradycardia (P < 0.001), whereas in SHR slight acceleration of heart rate was observed. In series 2 hemorrhage resulted in a small but significant increase o f mean arterial pressure (MAP; P < 0.05) and considerable tachycardia (P < 0.001). In SHR, L-NNA did not modify the decrease of MAP during h ypovolemia, and bleeding resulted in a significant bradycardia (P < 0. 001). Pretreatment with L-Arg in series 3 was able to reverse the effe cts of L-NNA on changes of MAP and heart rate during hypovolemia. The results indicate that the central nitroxidergic system plays a signifi cant role in eliciting hypotension and bradycardia in normotensive WKY during hemorrhage. Function of the central nitroxidergic system is si gnificantly altered in SHR in which NO appears to prevent hemorrhagic bradycardia and to reduce the hypotensive effect.