We conclude that cGMP-dependent signals activate SERCA via a protein kinase G-dependent phosphorylation of phospholamban. The increase in SERCA activity seems to reduce peak [Ca(2+)](i) and [Ca(2+)](i) oscillation during reoxygenation and to attenuate the excessive activation of the contractile machinery that otherwise leads to the development of hypercontracture.

✓ Application of Burton's concept of the critical closing pressure to experimental data on brain-blood flow in the monkey suggests that perfusion pressure, not vascular bed resistance, is the primary variable affecting cerebral blood flow. Perfusion pressure for the cerebral circulation is the mean arterial pressure minus the critical closing pressure (MAP — CCP). Vasomotor tone and intracranial pressure are the major determinants of the critical closing pressure. Changes in either of these variables, therefore, affect perfusion pressure and flow. Data on brain-blood flow at fixed vasomotor tone obtained over wide pressure ranges show little change in vascular bed resistance despite significant changes in flow. The diameter of resistance vessels probably does not change significantly throughout the normal physiological range of cerebral blood flow. The limits of the critical closing pressure in the anesthetized monkey are from 10 to 95 mm Hg. Using these limits, and beginning with the average values for MAP and CCP in 11 awake monkeys breathing room air, the authors present theoretical flow curves in response to changes in intracranial pressure and mean arterial pressure that closely approximate the data reported in man.

Experiments on 12 anesthetized dogs were performed to study the effects of changes in blood volume on the pulsatile hemodynamics of the arterial system as seen from its input. Pressure and flow were measured in the ascending aorta under control conditions, after volume expansion with dextran 70 (+30% of estimated blood volume), and after hemorrhage (-15% of estimated blood volume). The input inpedance of the arterial system was calculated for each condition. It was found that after volume expansion the characteristic impedance of the proximal aorta, Zc, was decreased by 26.6 +/- 5.1% (SE) (P less than 0.01). After hemorrhage Zc was increased by 30.4 +/- 3.4% (P less than 0.01). Since it is well known that Zc is a very weak function of the mean arterial pressure, it is concluded that the changes in Zc seen with volume expansion or hemorrhage are caused mainly by changes in aortic smooth muscle activity. This conclusion is also supported by direct measurements of aortic pressure diameter relationships in earlier work from our lab.

✓ Pressure-flow data are presented for the brain vascular bed in the rhesus monkey. These data are obtained at fixed levels of vasomotor tone. Resultant flow curves are called the “dynamic pressure-flow relationships” (DPFR). In the experimental model, arterial pressures are oscillated with a sinusoidal pump at frequencies exceeding the vasomotor response lag time. The resultant DPFR curves are discussed. A model is presented to show that changes in vasomotor tone cause a vertical shift of the DPFR. Changes in vascular bed resistance cause a change in the slope of the DPFR (▵P/▵F).

Experiments were performed on eight anesthetized dogs to study the response of the characteristic impedance (Zc) of the main pulmonary artery to changes in circulating blood volume. Pressure and flow were measured in the proximal main pulmonary artery under control conditions, after hemorrhage (-15% of the estimated blood volume), again under control conditions, and finally after volume expansion (+30% of the estimated blood volume). Two different methods were used to determine Zc from these recordings. With the frequency-domain method values for Zc were obtained by averaging the input impedance moduli between 2 and 15 Hz. With the time-domain method Zc was derived as the slope of the early ejection pressure-flow relationship. The values for Zc obtained with the two methods were not statistically different. In the time-domain method the average increase in Zc with hemorrhage was 30.7 +/- 7.4 (SE) %, and the average decrease with volume expansion was -21.1 +/- 5.0 (SE) %. Because the time-domain method allowed the values of Zc during control conditions and after hemorrhage to be obtained in the same pressure range, it was concluded that the observed changes were caused by a change in the activity of the smooth muscle in the pulmonary arterial wall. Similarly, it was concluded that the decrease in Zc after volume expansion was active in nature.