Functional defects in purinergic neurotransmission, and specifically adenosine A1 receptor, have been implicated in the development of hypertension in spontaneously hypertensive rats (SHR). Here, we examined the role of adenosine receptors in regulating cerebrovascular function in pre-hypertensive SHR.Design and Method:
Changes in the diameter of pial arterioles (20–100 μm) in response to adenosine A1 and A2 receptor agonists were assessed after pre-constriction with the thromboxane agonist U46619 in slices from the brainstem and cortex of 4–6 week-old Wistar and SHR.Results:
U46619 (200 nM) induced a similar vasoconstriction in arterioles from Wistar and SHR. In brainstem slices, adenosine (10 μM) reversed the U46619-induced vasoconstriction by 39 ± 5% in Wistars but not SHR (6 ± 3%, n = 5–7, p < 0.05). In contrast, in cortical slices, the vasodilator efficiency of adenosine was similar between Wistar and SHR (48 ± 8% and 40 ± 6%, respectively, n = 9). Likewise, the selective A2A agonist (CGS-21680, 1 μM) dilated pre-constricted brainstem arterioles from Wistar but not SHR (38 ± 8% vs −5 ± 5%, respectively, n = 5, p < 0.01), while its vasodilator efficiency in the cortex was similar between strains (38 ± 8% and 42 ± 10%, respectively, n = 7). The vasodilator efficiency of the A1/A2 agonist (5’-N-ethylcarboxamidoadenosine, 1 μM) was also greater in brainstem slices from Wistar than SHR (26 ± 15% vs 9 ± 2%, respectively, n = 6), while its efficiency in cortical slices was similar between strains (57 ± 13% and 50 ± 12%, respectively, n = 7). In contrast, the A1 receptor agonist CPA (1 μM) produced moderate vasoconstriction in the brainstem of Wistar and SHR (−19 ± 8% and −26 ± 10%, respectively, n = 5), but no change in the cortex (+14 ± 16% vs + 2 ± 8%, respectively).Conclusions:
These results suggest that the vasodilator efficiency of adenosine A2A receptors is markedly reduced in the brainstem but not cortical pial arterioles of pre-hypertensive SHR. This brainstem-specific deficiency in adenosine signalling could potentially lead to brainstem hypoperfusion and contribute to hypertension in SHR. British Heart Foundation, MRC and BBSRC funded research.