RPR101511A, which acts by inhibition of the PDGFr-TK, completely prevented angiographic loss of gain following PTCA and significantly reduced histological intimal hyperplasia.

Adenosine is known to produce cardiovascular effects such as bradycardia and hypotension via activation of myocardial (A₁) and vascular (A₂) receptors and antilipolytic effects through activation of adipocyte (A₁) receptors. We established the cardiovascular and antilipolytic profile of the adenosine A₁ agonist GR79236 (N⁶-[(lS, trans)-2-hydroxycyclopentyl]-adenosine) and compared it with CPA (N⁶-cyclopentyl-adenosine). GR79236 was approximately 3-fold less potent than CPA in inhibiting in vitro lipolysis. In conscious rats, both agents were shown to have antilipolytic and glucose-lowering properties. In rats instrumented with telemetry transmitters, orally administered CPA was one log unit more potent than GR79236 as a hypotensive and bradycardic agent. In summary, GR79236 is an A₁-selective adenosine agonist which reduces heart rate and mean arterial pressure and produces decreased plasma lipids and glucose levels.

The effect of cGMP and cGMP-dependent protein kinase (cG-PK) on contraction and relaxation was studied in skinned smooth muscle fibers from guinea pig taenia coli and chicken gizzard. At a fixed [Ca2+] relaxation was significantly enhanced by activated cG-PK in fibers from guinea pig taenia coli, but not in those from chicken gizzard. The Ca2+-requirement for half maximal tension maintenance was shifted to the right. Relaxation was associated with a decline in phosphorylated myosin light chain-2 from 34% to 25%. Similarly to relaxation activated cG-PK inhibited tension development only in fibers from taenia coli. These results suggest that mammalian and chicken smooth muscle fibers respond differently to cG-PK.

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The relationship between glycogen phosphorylase activity (an index of cytosolic Ca2+ content), myosin light-chain phosphorylation, isotonic shortening velocity, and isometric tension was examined in canine trachealis. Responses were measured in tracheal strips contracted with various concentrations of methacholine or K+. Both agonists produced prolonged and concentration-dependent increases in isometric tension that reached 90% of the plateau level within 1 (methacholine) to 5 (K+) min and remained stable over 60 min. In contrast to the monotonic increase in isometric tension, shortening velocity reached a maximum almost immediately (12-48 s) after the addition of either methacholine or K+ and then declined over time to a steady-state level that was 25-40% of the peak. Phosphorylase activity also increased transiently, reaching a maximum 1-2 min after the addition of either agonist before declining to near-basal levels over the 60-min observation period. Unlike the increases in shortening velocity and phosphorylase activity, agonist-induced myosin phosphorylation was not markedly transient. Moreover, regardless of the contractile agonist used, no correlation was found between myosin phosphorylation and shortening velocity when these parameters were compared at corresponding time points. This suggests that myosin phosphorylation is not the sole determinant of shortening velocity in canine trachealis.