Peripheral vascular smooth muscle relaxation in normotensive and hypertensive rats †

The adenylcyclase-phosphodiesterase system has been suggested as one of the biochemical mechanisms participating in the regulation of arterial tone and reactivity (Volicer & Hynie 1971; Triner et a1 1972). Specific alterations in the vascular cyclic nucleotides system have been advanced as an explanation for increased total peripheral resistance occurring in hypertension (Amer 1973, 1975). Cyclic nucleotides and ,Gadrenoceptor stimulants effect a decrease in the relaxation of aortic strips of spontaneously hypertensive (SH) rats compared with those of normotensive rats and defects in vascular relaxation have been proposed to contribute to hypertension (Triner et a1 1975, Cohen & Berkowitz 1976), while Spector et al (1969) have reported an enhanced relaxation in response to isoprenaline. As the aorta is not the major determinant factor of the total peripheral resistance, it is difficult to extrapolate the results obtained from these studies to small arteries and arterioles which are important in determining the level of blood pressure. I n view of these findings, studies were carried out to investigate the vasodilator activities of agents known to increase cyclic(c) AMP content of the tissues in the mesenteric vascular bed of SH, renal hypertensive (RH) and deoxycorticosterone acetate/saline hypertensive (docalsaline) rats. Male SH rats were direct descendants of the original strain developed by Okamoto & Aoki (1963). For renal hypertension, male Wistar rats were made hypertensive by clamping the left renal artery with silver clip (aperture 0.2 mm), leaving thc contralatcral kidncy intact (Goldblatt et a1 1934). Mineralocorticoid hypertension was induced in male Wistar rats by implanting 4 pellets (25 mg each) of doca, subcutaneously after removing the left kidney and substituting 1.0% sodium chloride solution for drinking water (Peterfalvi & Jequier 1960). For the purpose of comparison, age matched normotensive Wistar Kyoto (WKY) rats, and sham operated age matched normotensive Wistar (NW) rats were used as controls respectively (Lais & Brody 1978). The age, weight, blood pressure and ratio of the weight of ventricles to body weight of the animals are summarized in Table 1. Since isoprenaline, papaverine and adenosine are known to cause relaxation of arterial smooth muscle by increasing tissue CAMP content either by stimulating adenylcyclase or by inhibiting phosphodiesterase (Poch & Kukovetz 1971 ; Wurm et a1 1976), the vasodilator effects of these agents were investigated on