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VOL. 69 (4) ADENOSINE RECEPTORS

2001). Somewhat more surprising was the finding that there was a clear
hyperalgesia in these animals. This clearly suggests that adenosine acting
at A1 receptors constitute a significant endogenous analgesic mechanism.

The actions of adenosine are however mediated also by other adenosine
receptors. Thus adenosine A2A rerceptors, presumably located at sensory
nerve endings, medate hyperalgesia (Ledent et al.; 1997). A3 receptors are
– at least in mice – important as promoters of peripheral inflammation
that leads to pain.

It has long been known that adenosine can decrease cardiac performance
and reduce heart rate (Drury and Szent-György; 1929), and this effect,
which is clinically relevant, is linked to A1 receptors. The depressant
effect of exogenous adenosine analogues was virtually eliminated in A1R
-/- mice. It was therefore surprising that heart rate in A1R -/- mice proved
to be similar to that in their wild type littermates.

Blood pressure in anaesthetised mice was elevated in the A1R -/-
genotype (12 mm Hg), and there was even a tendency towards an elevated
blood pressure in A1R +/- mice ( 5 mm Hg) (Brown, Ollerstam,
Johansson, Skött, Fredholm and Persson; 2001). Since A1R -/- mice also
had an elevated level of plasma renin a possible explanation is that the
blood pressure elevation is due to angiotensin. However, an antagonist
did not differ in its blood pressure lowering effect between genotypes
(Brown, Ollerstam, Johansson, Skött, Fredholm and Persson; 2001).
There were no major differences in blood vessel reactivity between
genotypes, so we are still looking for the cause of the blood pressure
increase. Given that the A2AR -/- genotype is also hypertensive (Ledent
et al.; 1997) it will be interesting to know if the double knock-out shows a
marked blood pressure elevation.

In preliminary studies we have found that isolated hearts from A1R -/-
mice do not differ in their response to acute ischemia from hearts from
their wild type littermates. However, we do see a markedly reduced
protective effect of remote preconditioning. Ongoing studies aims at
demonstrating the underlying mechanisms.

Sodium excretion was markedly (two-fold) elevated in both A1R +/- and -
/- mouse kidneys (Brown, Ollerstam, Johansson, Skött, Fredholm and

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