Presynaptic a- and /3-Adrenoceptor Stimulation and Norepinephrine Release in the Spontaneously Hypertensive Rat

The present study was designed to measure norepinephrine release during sympathetic nerve stimulation and evaluate the presynaptic inhibitory and facilitatory actions of a-adrenoceptor and /3-adrenoceptor agonists respectively, in the isolated perfused kidney of normotensive WistarKyoto (WKY) and spontaneously hypertensive rats (SHR). Periarterial nerve stimulation (0.25 to 32 Hz) caused a significantly greater release of norepinephrine, which was measured as total tritium overflow, in the SHR. The vasoconstrictor responses to periarterial nerve stimulation as well as to norepinephrine, angiotensin II, and barium chloride were also significantly greater in the SHR. Presynaptic actions of tramazoltne, an a2-adrenoceptor agonist, and salbutamol, a /32-adrenoceptor agonist, on norepinephrine release were determined during periarterial nerve stimulation at 2 Hz. Tramazoline (2 x 10~ to 2 x 10" M) caused a concentration-dependent inhibition of stimulusinduced release of norepinephrine in SHR but not in WKY. While the highest concentration of tramazoline (2 x 10" M) exerted an inhibitory action in the WKY, this effect was of lesser magnitude than that seen in SHR. Salbutamol (10~ to 10~ M) produced an increase in norepinephrine release during periarterial nerve stimulation; however, this action of the /3-adrenoceptor agonist was similar in both the WKYand SHR. These results demonstrate that norepinephrine release during sympathetic nerve stimulation is significantly greater in the SHR, and this phenomenon may contribute to the maintenance of hypertension. While presynaptic /3-adrenoceptor function is similar in both the WKY and SHR, presynaptic a-adrenoceptors are supersensitive in the SHR. This supersensitivity may be of physiological importance in curtailing an already greater release of norepinephrine present in the SHR. (Hypertension 5: 198-204, 1983)