In the aortas and mesenteric arteries from spontaneous hypertensive rats and in the aortas from stress-and desoxycorticosterone-acetate-hypertensive rats, the intracellular cGMP: cAMP ratios were significantly elevated when compared to the ratios in the aortas of the respective controls. Decreases in the intracellular cAMP or cGMP levels were consistently associated with increased activity of the cyclic-nucleotide-specific low Km phosphodiesterase (3': 5'. Previous studies from this laboratory have indicated that the aortas from spontaneous and stress hypertensive rats (1) and more recently from neurogenically hypertensive rats (2) contained lesser amounts of 3': 5'-cAMP due primarily to increased rates of hydrolysis of the cyclic nucleotide. The decrease in the intracellular levels of cAMP was proposed as a possible mechanism for the increased vascular resistance and the vascular smooth muscle changes associated with the three rat models of hypertension.In the present work, studies were conducted with tissues from rats made hypertensive by combined desoxycorticosterone acetate (DOCA) and salt administration. The role of 3': 5'-cGMP, the other naturally occurring cyclic nucleotide, which is now being considered as an important partner for cAMP in the control of cellular function (3-5), was also investigated. MATERIALS AND METHODSSpontaneous and stress hypertensive rats and their respective controls were obtained as previously described (1). DOCAhypertensive rats were prepared as described by Stanton and White (6). Systolic blood pressures were determined indirectly by the tail cuff technique and were 192 ± 3, 165 + 4, and 226 + 1 mm Hg for the spontaneous, stress, and DOCA-hypertensive rats, respectively. Control rats for those same groups had pressures of 130 + 2, 125 A 2, and 132 4 2 mm Hg, respectively. Values are i SEM.Most of the experiments were carried out on the aortas, mesenteric arteries, and hearts removed from the animals immediately after their decapitation. A portion of each tissue (20-30 mg) was immediately frozen in liquid nitrogen and kept frozen at -20°until analyzed for cyclic nucleotide contents within 2 weeks. The remainder of the fresh tissue was homogenized in 4 volumes of ice-cold isotonic sucrose, kept at 40, and assayed for pertinent enzyme activities within 2 hr.The aortas and mesenteric arteries from two to four animals were combined into each sample. cAMP and cGMP levels and phosphodiesterase (PDE, 3': 5'-cAMP 5'-nucleotidohydrolase, EC 3.1.4.17) adenylyl cyclase [AC, ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1] and guanylyl cyclase [GC, GTP pyrophosphate-lyase (cyclizing), EC 4.6.1.2] activities were determined as described previously (1,7). The cyclic nucleotide index was calculated according to the formula: cAMP content in control cAMP content in hypertensive cGMP content in control cGMP content in hypertensive RESULTSIn the spontaneously hypertensive rat the aortas contained significantly less cAMP and more cGMP than did the control aortas (Table 1). Aortas of stress ...

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A reliable diagnosis of PAD can be made using the ankle-brachial index (ABI). This is a simple, noninvasive and reasonably accurate screening recommended in all diabetic individuals >50 years of age. However, ABI measurement has its drawbacks because medial calcification of the tibial arteries making them non-compressible, resulting in unusually